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81.
Ushiroda K Maruta K Kitoh M Iwai K Nagamine J Tsuchida A Taiji M Nagata R 《Bioorganic & medicinal chemistry letters》2011,21(1):220-224
Starting with a subtle blood glucose-lowering effect of a TGF-β inhibitor, we designed and synthesized a series of benzoylpyrrole-based carboxylic acids as PPARs activators. Among these compounds, 10sNa exhibited favorable blood glucose-lowering effect without body weight gain. We assume that the beneficial effect of 10sNa is attributed to not only its compound PPARα agonistic activity but also its PPARγ partial agonistic activity. 相似文献
82.
Miyuki Bohgaki Masaki Matsumoto Tatsuya Atsumi Takeshi Kondo Shinsuke Yasuda Tetsuya Horita Keiichi I. Nakayama Fumihiko Okumura Shigetsugu Hatakeyama Takao Koike 《Journal of cellular and molecular medicine》2011,15(1):141-151
Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL) that directly recognizes plasma β2‐glycoprotein I (β2GPI). Tissue factor (TF), the major initiator of the extrinsic coagulation system, is induced on monocytes by aPL in vitro, explaining in part the pathophysiology in APS. We previously reported that the mitogen‐activated protein kinase (MAPK) pathway plays an important role in aPL‐induced TF expression on monocytes. In this study, we identified plasma gelsolin as a protein associated with β2GPI by using immunoaffinity chromatography and mass spectrometric analysis. An in vivo binding assay showed that endogenous β2GPI interacts with plasma gelsolin, which binds to integrin a5β1 through fibronectin. The tethering of β2GPI to monoclonal anti‐β2GPI autoantibody on the cell surface was enhanced in the presence of plasma gelsolin. Immunoblot analysis demonstrated that p38 MAPK protein was phosphorylated by monoclonal anti‐β2GPI antibody treatment, and its phosphorylation was attenuated in the presence of anti‐integrin a5β1 antibody. Furthermore, focal adhesion kinase, a downstream molecule of the fibronectin‐integrin signalling pathway, was phosphorylated by anti‐β2GPI antibody treatment. These results indicate that molecules including gelsolin and integrin are involved in the anti‐β2GPI antibody‐induced MAPK pathway on monocytes and that integrin is a possible therapeutic target to modify a prothrombotic state in patients with APS. 相似文献
83.
Yoshida T Kimura E Koike S Nojima J Futai E Sasagawa N Watanabe Y Ishiura S 《International journal of biological sciences》2011,7(3):301-307
Various vaccine therapies for Alzheimer's disease (AD) have been investigated. Here we report transgenic rice expressing amyloid β-peptide (Aβ). The Aβ42 gene fused with a green fluorescent protein gene was introduced into rice using the Agrobacterium method. When transgenic brown rice expressing Aβ was orally administered to mice, serum anti-Aβ antibody titers were elevated. The same results were observed when mice were fed boiled, transgenic brown rice. The results indicate that an edible vaccine against AD using rice may be feasible. A vaccine derived from rice would be far cheaper than existing medical vaccines. 相似文献
84.
85.
Keita Komine Yasuhiro Urayama Taku Hosaka Hayato Fukuda Susumi Hatakeyama Jun Ishihara 《Chirality》2020,32(3):273-281
Enantioselective formation of cyclohexene derivatives bearing an all-carbon quaternary stereogenic center is described. The racemic cyclohexenes are readily transformed to chiral substituted cyclohexenes in good yield with excellent enantioselectivity and diastereoselectivity by a palladium-mediated deracemization. The resulting products are promising synthetic intermediates of biologically active natural products. This protocol provides us with a new entry to the concise and scalable synthesis of multifunctionalized compounds. 相似文献
86.
A new method is presented for determining the hydration site of proteins, where the effect of structural fluctuations in both protein and hydration water is explicitly considered by using molecular dynamics simulation (MDS). The whole hydration sites (HS) of lysozyme are composed of 195 single HSs and 38 clustered ones (CHS), and divided into 231 external HSs (EHS) and 2 internal ones (IHS). The largest CHSs, ‘Hg’ and ‘Lβ’, are the IHSs having 2.54 and 1.35 mean internal hydration waters respectively. The largest EHS, ‘Clft’, is located in the cleft region. The real hydration structure of a CHS is an ensemble of multiple structures. The transition between two structures occurs through recombinations of some H-bonds. The number of the experimental X-ray crystal waters is nearly the same as that of the estimated MDS hydration waters for 70% of the HSs, but significantly different for the rest of HSs. 相似文献
87.
88.
Suzuki H Ikeda N Kobayashi K Terashima Y Shimada Y Suzuki T Hagiwara T Hatakeyama S Nagaoka K Yoshida J Saito Y Tanaka J Hayashi M 《Mutation research》2005,583(2):133-145
We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens-4,4'-methylenedianiline (MDA), quinoline, o-toluidine, 4-chloro-o-phenylenediamine (CPDA), dimethylnitrosamine (DMN), p-dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)-and two mutagenic chemicals-kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o-toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o-Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual. 相似文献
89.
Harada H Morozumi K Nashihara H Hatakeyama E 《Journal of PHYSIOLOGICAL ANTHROPOLOGY and Applied Human Science》2005,24(4):383-388
This paper investigates the applicability of cerebral blood flow in evaluating the technological adaptability for operating industrial products. The procedure of the experiment was explained to the subjects and informed consent was obtained from them. Twenty male and twenty female subjects (19-22 yrs) operated the destination setting task of a car navigation system. Subjects were divided into two sub groups to operate tasks of model A and model B of a car navigation system. Operation time of tasks and cerebral blood flow of frontal region were measured during tasks. Non-invasive measuring of regional cerebral blood flow was estimated by measuring deoxygenated hemoglobin, oxygenated hemoglobin, and total haemoglobin using the time resolved spectroscopy (TRS). Females were faster than males in operating the task of setting the destination searched by street address. Total haemoglobin of male subjects was significantly higher than that of females during resting and tasks. Changes of cerebral blood flow were observed during operating a car navigation system. In this paper we discussed the possibility of physiological evaluation for technological adaptability by means of the performance and brain hemodynamics measurement. 相似文献
90.
Yajima K Shirai Y Fujita N Sato D Umezu H Hatakeyama K 《World journal of surgical oncology》2005,3(1):14-3
BACKGROUND: Subcutaneous leiomyosarcoma is a rare condition that accounts for 1% to 2% of all superficial soft tissue malignancies. Approximately 10% of cases arise in the trunk, although the extremities are the most commonly affected. CASE PRESENTATION: We report herein the case of a 31-year-old man with a subcutaneous leiomyosarcoma, measuring 124 x 105 mm, arising in the left inguinal region. A wide local excision (with a resection margin >/= 20 mm) was performed. Histological examination of the resected specimen revealed a leiomyosarcoma with high cellularity and two mitoses per 10 high-power fields. The patient remains well with no evidence of disease 5 years and 8 months after the operation. CONCLUSION: This is the first reported case of subcutaneous leiomyosarcoma arising in the inguinal region and also one of the largest tumors reported. The experience of this case and a review of the English-language literature (PubMed, National Library of Medicine, Bethesda, MD, USA) suggest that a resection margin of >/= 10 mm is recommended when excising this rare tumor. 相似文献