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151.
Honda K Okamoto K Mochida Y Ishioka K Oka M Maesato K Ikee R Moriya H Hidaka S Ohtake T Doi K Fujita T Kobayashi S Noiri E 《American journal of physiology. Cell physiology》2011,301(6):C1423-C1430
Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT (P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group (P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF (P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy. 相似文献
152.
Yano M Watanabe K Yamamoto T Ikeda K Senokuchi T Lu M Kadomatsu T Tsukano H Ikawa M Okabe M Yamaoka S Okazaki T Umehara H Gotoh T Song WJ Node K Taguchi R Yamagata K Oike Y 《The Journal of biological chemistry》2011,286(5):3992-4002
Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we generated and analyzed SMS1-null mice. SMS1-null mice exhibited moderate neonatal lethality, reduced body weight, and loss of fat tissues mass, suggesting that they might have metabolic abnormality. Indeed, analysis on glucose metabolism revealed that they showed severe deficiencies in insulin secretion. Isolated mutant islets exhibited severely impaired ability to release insulin, dependent on glucose stimuli. Further analysis indicated that mitochondria in mutant islet cells cannot up-regulate ATP production in response to glucose. We also observed additional mitochondrial abnormalities, such as hyperpolarized membrane potential and increased levels of reactive oxygen species (ROS) in mutant islets. Finally, when SMS1-null mice were treated with the anti-oxidant N-acetyl cysteine, we observed partial recovery of insulin secretion, indicating that ROS overproduction underlies pancreatic β-cell dysfunction in SMS1-null mice. Altogether, our data suggest that SMS1 is important for controlling ROS generation, and that SMS1 is required for normal mitochondrial function and insulin secretion in pancreatic β-cells. 相似文献
153.
Takeharu Sakamoto Jane S. Weng Toshiro Hara Seiko Yoshino Hiroko Kozuka-Hata Masaaki Oyama Motoharu Seiki 《Molecular and cellular biology》2014,34(1):30-42
Hypoxia-inducible factor 1 (HIF-1) plays a key role in the cellular adaptation to hypoxia. Although HIF-1 is usually strongly suppressed by posttranslational mechanisms during normoxia, HIF-1 is active and enhances tumorigenicity in malignant tumor cells that express the membrane protease MT1-MMP. The cytoplasmic tail of MT1-MMP, which can bind a HIF-1 suppressor protein called factor inhibiting HIF-1 (FIH-1), promotes inhibition of FIH-1 by Mint3 during normoxia. To explore possible links between HIF-1 activation by MT1-MMP/Mint3 and tumor growth signals, we surveyed a panel of 252 signaling inhibitors. The mTOR inhibitor rapamycin was identified as a possible modulator, and it inhibited the mTOR-dependent phosphorylation of Mint3 that is required for FIH-1 inhibition. A mutant Mint3 protein that cannot be phosphorylated exhibited a reduced ability to inhibit FIH-1 and promoted tumor formation in mice. These data suggest a novel molecular link between the important hub proteins MT1-MMP and mTOR that contributes to tumor malignancy. 相似文献
154.
Reiji Kojima Tatsukuni Ohno Motoyasu Iikura Toshiro Niki Mitsuomi Hirashima Keichi Iwaya Hitoshi Tsuda Shigeaki Nonoyama Akio Matsuda Hirohisa Saito Kenji Matsumoto Susumu Nakae 《PloS one》2014,9(1)
Galectin-9 (Gal-9), a lectin having a β-galactoside-binding domain, can induce apoptosis of Th1 cells by binding to TIM-3. In addition, Gal-9 inhibits IgE/Ag-mediated degranulation of mast cell/basophilic cell lines by binding to IgE, thus blocking IgE/Ag complex formation. However, the role of Gal-9 in mast cell function in the absence of IgE is not fully understood. Here, we found that recombinant Gal-9 directly induced phosphorylation of Erk1/2 but not p38 MAPK in a human mast cell line, HMC-1, which does not express FcεRI. Gal-9 induced apoptosis and inhibited PMA/ionomycin-mediated degranulation of HMC-1 cells. On the other hand, Gal-9 induced cytokine and/or chemokine production by HMC-1 cells, dependent on activation of ERK1/2 but not p38 MAPK. In addition, the lectin activity of Gal-9 was required for Gal-9-mediated cytokine secretion by HMC-1 cells. These observations suggest that Gal-9 has dual properties as both a regulator and an activator of mast cells. 相似文献
155.
Tomohiro Komorita Rumiko Kajihara Hiroaki Tsutsumi Seiichiro Shibanuma Toshiro Yamada Shigeru Montani 《PloS one》2014,9(1)
The relationship between the food demand of a clam population (Ruditapes philippinarum (Adams & Reeve 1850)) and the isotopic contributions of potential food sources (phytoplankton, benthic diatoms, and organic matter derived from the sediment surface, seagrass, and seaweeds) to the clam diet were investigated. In particular, we investigated the manner in which dense patches of clams with high secondary productivity are sustained in a coastal lagoon ecosystem (Hichirippu Lagoon) in Hokkaido, Japan. Clam feeding behavior should affect material circulation in this lagoon owing to their high secondary productivity (ca. 130 g C m−2 yr−1). Phytoplankton were initially found to constitute 14–77% of the clam diet, although phytoplankton nitrogen content (1.79–4.48 kmol N) and the food demand of the clam (16.2 kmol N d–1) suggest that phytoplankton can constitute only up to 28% of clam dietary demands. However, use of isotopic signatures alone may be misleading. For example, the contribution of microphytobenthos (MPB) were estimated to be 0–68% on the basis of isotopic signatures but was subsequently shown to be 35±13% (mean ± S.D.) and 64±4% (mean ± S.D.) on the basis of phytoplankton biomass and clam food demand respectively, suggesting that MPB are the primary food source for clams. Thus, in the present study, the abundant MPB in the subtidal area appear to be a key food source for clams, suggesting that these MPB may sustain the high secondary production of the clam. 相似文献
156.
Motoko Oarada Hiroshi Furukawa Toshiro Majima Teruo Miyazawa 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2000,1487(1):1-14
The effect of dietary polyunsaturated fatty acids and α-tocopherol supplementation on erythrocyte lipid peroxidation and immunocompetent cells in mice was studied comparatively using seven dietary oils (15% oil/diet, w/w) including fish oil rich in eicosapentaenoic acid (EPA, 20:5, n–3) and docosahexaenoic acid (DHA, 22:6, n–3). A 43% increase in spleen weight, about twice as many spleen cells and no change in the subpopulations of spleen cells, as well as a significant depression of mitogen-induced blastogenesis of both T and B cells in the spleen were observed in mice fed fish oil for 30 days in comparison with soybean oil diet-fed mice. In the fish oil diet-fed mice, membranous lipid hydroperoxide (hydroperoxides of phosphatidylcholine and phosphatidylethanolamine) accumulation as a marker of oxidative senescence in red blood cells (RBC) was 2.7–3.5 times higher than that in mice fed soybean oil, although there was no difference in the plasma phosphatidylcholine hydroperoxide concentration. In spite of the supplementation of α-tocopherol to up to 10 times the level in the basal diet, the degeneration of spleen cells and the stimulated oxidative senescence of RBC found by the fish oil feeding could not be prevented. The results suggest that oral intake of excess polyunsaturated fatty acids, i.e. EPA and DHA, in a fish oil diet can lead to acceleration of membrane lipid peroxidation resulting in RBC senescence linked to the lowering of immune response of spleen cells, and that supplementation of α-tocopherol as antioxidant does not always effectively prevent such oxidative degeneration as observed in spleen cells and RBC in vivo. 相似文献
157.
The effect of administration of PSK (Polysaccharide Kureha), aColiolus preparation, in Meth-A solid tumors was analyzed in BALB/c mice. Spleen cells prepared from normal, non-treated Meth-A bearing, PSK-treated normal and PSK-treated tumor bearing mice were examined for induction of macrophage chemotactic factor (MCF). Only spleen cells from the latter mice produced MCF after 48 hrs of cultivation in the presence of Meth-A cells or Concanavalin A (Con A). MCF-producing cells were indicated to be Lyt-1 positive, L3T4 positive and Lyt-2 negative cells in the negative elimination assay. There were no differences in the production of other cytokines including interleukin-2, inferferon and tumor necrosing factor, spleen cells obtained other different groups of mice. The antitumor effect of either crude or purified MCF (molecular weight 100,000) was examined by daily consecutive intratumoral injections into Meth-A tumor tissues, and a significant inhibitory effect was detected. 相似文献
158.
Immunopotentiator separated from hot water extract of the seed of Benincasa cerifera Savi (Tohgashi)
Yoshio Kumazawa Yoko Nakatsuru Akira Yamada Toshio Yadomae Chiaki Nishimura Yasuo Otsuka Kikuo Nomoto 《Cancer immunology, immunotherapy : CII》1985,19(2):79-84
Summary The separation and properties of a new immunopotentiator, Benincasa cerifera mitogen (BCM) fraction, were investigated. BCM fraction was separated from hot water extract of the seed of Benincasa cerifera Savi (Tohgashi) by gel filtration using Sepharose 4B. BCM fraction is a heteropolymer consisting of uronic acid, neutral sugars, protein, and phosphorus. The proliferation and differentiation of murine B cells were markedly stimulated by BCM fraction. The in vitro development of peritoneal macrophages into antitumor macrophages was also activated by the addition of BCM fraction to cultures. BCM fraction augmented the IgM and IgG antibody responses against sheep erythrocytes (SRBC) and the induction of delayed-type footpad reaction against SRBC. The antitumor activity of BCM fraction was observed in terms of prolongation of the survival period of mice bearing Meth A fibrosarcoma. After hydrolysis with 1% acetic acid at 100° C for 4 h, marked mitogenic activity was found in a precipitate composed of 29% neutral sugars, 50% uronic acid, 1% protein, and 0.1% phosphorus. The precipitate did not contain detectable amino sugar. The possibility that the biological activities of BCM fraction may be due to contamination by bacterial lipopoly-saccharide was ruled out on the basis of the results of chemical analysis and of marked mitogenicity noted in C3H/HeJ spleen cell cultures.
Abbreviations used: BCM, Benincasa cerifera mitogen; SRBC, sheep erythrocytes; PFC, plaque-forming cells; TNP-HRBC, trinitrophenylated horse erythrocytes; PBA, polyclonal B-cell activation; SI, stimulation index 相似文献
159.
Toshiro Tsubouchi Masashi Yagi Iori Sumida Keisuke Tamari Yuji Seo Kazuhiko Ogawa 《Reports of Practical Oncology and Radiotherapy》2018,23(5):425-432
Aim
To evaluate the influence of the beam shape created by X-rays with “flat beams” and without “flattening-filter-free [FFF] beams” a flattening filter, and the isocenter locations for FFF beams on the treatment of a large irradiated volume for tumours.Background
The increase of dose rate and the decrease of out-of-field dose can be expected for FFF beams and lead to effective and safety radiotherapy. On the other hand, the bell-shaped dose profile is thought to be a factor of negating these advantages.Materials and methods
Treatment plans for 15 patients with head and neck cancer were created using XiO (Elekta, Stockholm AB, Sweden) in fixed-gantry step-and-shoot delivery under the same dose constraints. Seven fields of FFF beams with 7?MV and flat beams with 6?MV were used with the technique of intensity-modulated radiation therapy (IMRT). We compared the dose homogeneity and conformity of targets and dose constraints for organs as the plan quality and evaluated physical parameters: monitor unit (MU) values, number of segments and their locations from the isocenter in beam's-eye-view.Results
No significant differences were found in the plan quality. The isocenter locations do not affect the physical parameters for FFF beams. It has been confirmed that the number of segments and MU values were 40% higher with FFF beams than with flat beams (p?<?0.05).Conclusion
This study demonstrates flat dose distribution is more suitable for IMRT with large and complex targets. 相似文献160.
Early detection of gastric cancer after Helicobacter pylori eradication due to endoscopic surveillance
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Kosuke Sakitani Toshihiro Nishizawa Masahide Arita Shuntaro Yoshida Yosuke Kataoka Daisuke Ohki Hiroharu Yamashita Yoshihiro Isomura Akira Toyoshima Hidenobu Watanabe Toshiro Iizuka Yutaka Saito Junko Fujisaki Naohisa Yahagi Kazuhiko Koike Osamu Toyoshima 《Helicobacter》2018,23(4)