Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
33 巻 , 6 号
December
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
  • Yoshifumi Kadono, Sotaro Miwa, Takashi Shima, Hiroyuki Konaka, Atsushi ...
    2012 年 33 巻 6 号 p. 323-328
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    Interferon-alpha (IFN-α) has been used in systemic treatment for metastatic renal cell carcinoma (mRCC). IFN-α has at least 14 subtypes, each of which has different biological activity. There have been reports that mRCC resistant to an IFN-α treatment responded to another IFN-α subtype. This study was performed to evaluate the effectiveness of alternation of different IFN-α subtypes for mRCC that did not respond to initial IFN-α treatment. In our department and associated institutions, alternating therapy of IFN-α was provided for 15 initial IFN-α refractory mRCC cases from June 2005 to September 2008. Among the 15 patients, the effects of alternating IFN-α therapy were as follows: complete response (CR), 0 cases; partial response (PR), 1 case; stable disease (SD), 3 cases; progressive disease (PD), 11 cases. The response rate (CR+PR) was 7% and disease control rate (CR+PR+SD) was 27%. No severe side effects were observed in any of these cases. The PR case is still in PR 21 months after alternating IFN-α therapy. Among the three SD cases, one has continued SD for 14 months and the other for 12 months. Alternating IFN-α therapy for mRCC can be attempted even if other cytokines are not effective.
  • Erwin Suwendi, Hitoshi Iwaya, Jae-Sung Lee, Hiroshi Hara, Satoshi Ishi ...
    2012 年 33 巻 6 号 p. 329-336
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    Dextran sulfate sodium (DSS)-induced colitis is an experimental model of ulcerative colitis, although the precise mechanism has not yet been elucidated. We investigate whether Zn deficiency affects the pathogenesis of colitis induced by DSS with a focus on immune responses. Male WKAH/Hkm Slc rats were fed either a Zn-adequate (ZA, 30 mg Zn/kg diet) as a control or Zndeficient (ZD, 5 mg Zn/kg diet) diet for 21 days and then treated with 2% DSS via deionized drinking water for 7 days. The disease activity index (DAI) was recorded daily throughout DSS treatment. Serum Zn concentrations were significantly lowered in rats fed the ZD diet than those fed the ZA diet at day 7 and 14. Surprisingly, DSS treatment considerably reduced the serum Zn in both groups. The rats fed the ZD diet showed exacerbated colitis based on clinical outcomes, including weight loss, increased DAI, and shortened colon length. An in vitro study corroborated these results, showing that a large amount of TNFα was induced by rat mesenteric leukocytes in response to lipopolysaccharide in ZD medium, but not in ZA medium. These results indicate that a modulation of TNFα production due to Zn deficiency influences disease activity in DSS-induced colitis. In addition, more attention should be given to Zn for prevention of colitis.
  • Kazuto Yamazaki, Kazuma Takase, Misako Watanabe, Takaki Kagaya, Hiroki ...
    2012 年 33 巻 6 号 p. 337-344
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP- 2R), a class-B G protein-coupled receptor (GPCR) coupled with Gαs. Few small-molecule agonists had been reported for class-B GPCRs, but we recently reported the first scaffold compounds of ago-allosteric modulators for human GLP-2R. Methyl 2-{[(2Z)-2-(2,5-dichlorothiophen- 3-yl)-2-(hydroxyimino)ethyl]sulfanyl}benzoate (compound 1) and its de-esterified derivative (compound 2) induced placental alkaline phosphatase (PLAP) activity in HEK293 cells overexpressing human GLP-2R and PLAP driven by cAMP response element. In this study, we observed that rat, Syrian hamster, and dog GLP-2Rs also responded to compounds 1 and 2 in the same reporter system. However, no agonistic activity of the compounds toward mouse GLP-2R was detected. Mutagenesis studies showed that mutant human GLP-2Rs with Pro392Leu substitution of mouse GLP-2R for human GLP-2R amino acid residues nullified the PLAP activity of compound 2, although these mutant receptors responded to GLP-2. This finding suggests that the Pro392 residue of human GLP-2R is essential for the agonistic activity of compound 2.
  • Ken Iseki, Seita Hagino, Takuya Nikaido, Yuxiang Zhang, Tetsuji Mori, ...
    2012 年 33 巻 6 号 p. 345-353
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    OASIS gene, a member of the CREB/ATF transcription factor family, is upregulated in gliosis after CNS injury. However it remains to be determined how OASIS is implicated in gliotic reaction. In a glial scar, chondroitin sulfate proteoglycans (CSPGs) are also upregulated, which engenders the inhibition of axonal regeneration. We investigated the functional role of OASIS in gliosis in relation to CSPG core proteins that render lesions non-permissive for regenerating axons. We first examined the gene expression localization of OASIS using several markers in a cryo-injured mouse brain and compared the expression pattern of CSPG core protein genes with that of OASIS in a glial scar by double-labeling in situ hybridization. Our findings suggest that OASIS is induced in proximal reactive astrocytes that exhibit upregulated expression for CSPGs, including NG2 proteoglycan, versican, brevican, neurocan, and phosphacan core. Furthermore, the membrane fraction derived from OASIS-transfected C6 cells inhibits neurite outgrowth of NG108-15 cells, whereas its neurite outgrowth inhibitory effect is abrogated after chondroitinase ABC treatment. OASIS is likely to be involved in the regulatory mechanism of non-permissive environments for axonal outgrowth.
  • Yoshinao Z Hosaka, Mika Ishibashi, Jun-ichi Wakamatsu, Masato Uehara, ...
    2012 年 33 巻 6 号 p. 355-361
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    The aim of this study was to clarify the effects of myostatin, which is a negative regulator of skeletal muscle mass, on the proliferation of NIH3T3 fibroblasts and the synthesis of extracellular matrix (ECM) by them. A proliferation assay revealed that myostatin attenuated cell growth at any of the doses used. High doses of myostatin strongly inhibited cell proliferation. Moreover, myostatin receptor, activin receptor type-2B (ActRIIB), was found to be distributed on cells and it was also clarified that myostatin increased the expression of cyclin-dependent kinase inhibitor p21 (p21). These results suggested that a high dose of myostatin inhibits fibroblast proliferation by the same mechanism as that for inhibition of myoblast proliferation. We then examined the effects of myostatin on the mRNA expression of ECM molecules (decorin, biglycan, type I collagen, type III collagen, type IV collagen and type V collagen) by real-time PCR. Real-time PCR showed that myostatin increased the mRNA of decorin, biglycan and collagen (types I, IV and V) in fibroblasts. The results suggest that myostatin regulates ECM synthesis in cultured fibroblasts.
  • Bao-Tran Anh Nguyen, Veronica Minkiewicz, Ellie McCabe, Jennifer Cecil ...
    2012 年 33 巻 6 号 p. 363-372
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    Inflammation is believed to play a role in uterine cervical remodeling and infection-induced preterm labor. One of the distinct features of remodeling uterine cervix is presence of prominent vascular events, such as angiogenesis, vasodilation, and vascular permeability. Although the functional significance of these features is not yet clear, we know that in most tissue types, vascular remodeling is intricately intertwined with inflammation. Since vascular endothelial growth factor (VEGF) is the major architect of vascular remodeling, we sought to examine and elucidate the potential relationship between VEGF and inflammation in the uterine cervix of non-pregnant mice. The animals used were divided into 4 treatment groups: A) negative control (vehicle only), B) positive control (lipopolysaccharide, LPS), C) recombinant VEGF-164 protein, and D) LPS + VEGF blocker (n = 3). After the appropriate treatments, the uterine cervices were harvested and analyzed using real-time PCR and confocal fluorescence microscopy. Results showed that exogenous VEGF upregulates expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNAs, whereas VEGF blocker partially diminishes the LPS-induced expression of pro-inflammatory factors compared to the positive control group. We conclude that a positive feed-forward relationship likely exists between VEGF and inflammation in the uterine cervix, thus implicating VEGF in inflammation-induced preterm labor.
Communication
  • Yoshihiko Hirotani, Ayae Doi, Tomoki Takahashi, Hanako Umezawa, Yoko U ...
    2012 年 33 巻 6 号 p. 373-376
    発行日: 2012年
    公開日: 2012/12/27
    ジャーナル フリー
    This study was designed to investigate the effect of an herbal medicine-goshajinkigan (GJ)-on the regulation of total body weight, as well as liver and adipose tissue weights in rats fed a highfat diet (HFD) and drinking of 30% sucrose (HFDS) (HFD; the rats received 19.6% energy from carbohydrates, 18.2% from proteins, and 62.2% from lipids; total energy, 506 kcal/100 g). Control rats were fed a standard diet (the rats received 60.5% energy from carbohydrates, 26.2% from proteins, and 13.3% from lipids; total energy, 360 kcal/100 g). Over a period of 12 weeks, rats were allowed free access to either the standard diet or HFDS containing 0, 1, or 3% GJ. In comparison with the control group, the HFDS rats showed a significant decrease in overall body weight and adipose tissue weight, and an increase in liver weight at 12 weeks. GJ treatment significantly reversed the HFDS-induced decrease in body and adipose tissue weight and reduced the elevated liver weight dose-dependently. Similarly, GJ reduced the elevated serum aspartate aminotransferase levels observed in HFDS rats. These results suggest that GJ may have the potential to alleviate damage to the liver in subjects with long-term consumption of HFDS.
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