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111.
112.
Kanae Oda Nobuyuki Miyatake Noriko Sakano Takeshi Saito Motohiko Miyachi Izumi Tabata Takeyuki Numata 《PloS one》2013,8(12)
Objective
To investigate the link between serum interleukin-18 (IL-18) levels and physical activity in Japanese men.Methods
A total of 81 men (45.7±17.6 years old) was enrolled in this cross-sectional investigation study. We assessed anthropometric and body composition parameters. Serum IL-18 levels, physical activity by uniaxial accelerometers, peak oxygen uptake and metabolic risk parameters were also evaluated.Results
Serum IL-18 levels were 179.4±84.7 pg/mL. Physical activity evaluated by Σ[metabolic equivalents × h per week (METs⋅h/w)]was significantly and negatively correlated with serum IL-18 levels (r = −0.252, p = 0.0235). These associations remained even after adjusting for age, peak oxygen uptake and other confounding factors.Conclusion
Serum IL-18 levels were closely associated with physical activity independent of peak oxygen uptake in Japanese men. 相似文献113.
Yoko Beniyama Kenji Matsuno Hiroyuki Miyachi 《Bioorganic & medicinal chemistry letters》2013,23(6):1662-1666
We designed a series of pyrazole-based carboxylic acids as candidate ligands of heart fatty acid binding protein (H-FABP, or FABP3), based on a comparison of the X-ray crystallographic structures of adipocyte fatty acid binding protein (FABP4)–selective inhibitor (BMS309403) complex and FABP3–elaidic acid complex. Some of the synthesized compounds exhibited dual FABP3/4 ligand activity, and some exhibited selectivity for FABP3. 相似文献
114.
Ban S Kasuga J Nakagome I Nobusada H Takayama F Hirono S Kawasaki H Hashimoto Y Miyachi H 《Bioorganic & medicinal chemistry》2011,19(10):3183-3191
A series of α-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) α-selective agonists, based on our PPARα/δ dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPARα agonistic activity and PPARα selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model. 相似文献
115.
Seishi Yamaguchi Junichiro Machida Munefumi Kamamoto Masashi Kimura Akio Shibata Tadashi Tatematsu Hitoshi Miyachi Yujiro Higashi Peter Jezewski Atsuo Nakayama Kazuo Shimozato Yoshihito Tokita 《PloS one》2014,9(8)
Since MSX1 and PAX9 are linked to the pathogenesis of nonsyndromic tooth agenesis, we performed detailed mutational analysis of these two genes sampled from Japanese patients. We identified two novel MSX1 variants with an amino acid substitution within the homeodomain; Thr174Ile (T174I) from a sporadic hypodontia case and Leu205Arg (L205R) from a familial oligodontia case. Both the Thr174 and Leu205 residues in the MSX1 homeodomain are highly conserved among different species. To define possible roles of mutations at these amino acids in the pathogenesis of nonsyndromic tooth agenesis, we performed several functional analyses. It has been demonstrated that MSX1 plays a pivotal role in hard tissue development as a suppressor for mesenchymal cell differentiation. To evaluate the suppression activity of the variants in mesenchymal cells, we used the myoD-promoter, which is one of convenient reporter assay system for MSX1. Although the gene products of these MSX1 variants are stable and capable of normal nuclear localization, they do not suppress myoD-promoter activity in differentiated C2C12 cells. To clarify the molecular mechanisms underlying our results, we performed further analyses including electrophoretic mobility shift assays, and co-immunoprecipitation assays to survey the molecular interactions between the mutant MSX1 proteins and the oligonucleotide DNA with MSX1 consensus binding motif or EZH2 methyltransferase. Since EZH2 is reported to interact with MSX1 and regulate MSX1 mediated gene suppression, we hypothesized that the T174I and L205R substitutions would impair this interaction. We conclude from the results of our experiments that the DNA binding ability of MSX1 is abolished by these two amino acid substitutions. This illustrates a causative role of the T174I and L205R MSX1 homeodomain mutations in tooth agenesis, and suggests that they may influence cell proliferation and differentiation resulting in lesser tooth germ formation in vivo. 相似文献
116.
Koji Iihara Kunihiro Nishimura Akiko Kada Jyoji Nakagawara Kuniaki Ogasawara Junichi Ono Yoshiaki Shiokawa Toru Aruga Shigeru Miyachi Izumi Nagata Kazunori Toyoda Shinya Matsuda Yoshihiro Miyamoto Akifumi Suzuki Koichi B. Ishikawa Hiroharu Kataoka Fumiaki Nakamura Satoru Kamitani 《PloS one》2014,9(5)
Background
The effectiveness of comprehensive stroke center (CSC) capabilities on stroke mortality remains uncertain. We performed a nationwide study to examine whether CSC capabilities influenced in-hospital mortality of patients with ischemic and hemorrhagic stroke.Methods and Results
Of the 1,369 certified training institutions in Japan, 749 hospitals responded to a questionnaire survey regarding CSC capabilities that queried the availability of personnel, diagnostic techniques, specific expertise, infrastructure, and educational components recommended for CSCs. Among the institutions that responded, data on patients hospitalized for stroke between April 1, 2010 and March 31, 2011 were obtained from the Japanese Diagnosis Procedure Combination database. In-hospital mortality was analyzed using hierarchical logistic regression analysis adjusted for age, sex, level of consciousness on admission, comorbidities, and the number of fulfilled CSC items in each component and in total. Data from 265 institutions and 53,170 emergency-hospitalized patients were analyzed. Mortality rates were 7.8% for patients with ischemic stroke, 16.8% for patients with intracerebral hemorrhage (ICH), and 28.1% for patients with subarachnoid hemorrhage (SAH). Mortality adjusted for age, sex, and level of consciousness was significantly correlated with personnel, infrastructural, educational, and total CSC scores in patients with ischemic stroke. Mortality was significantly correlated with diagnostic, educational, and total CSC scores in patients with ICH and with specific expertise, infrastructural, educational, and total CSC scores in patients with SAH.Conclusions
CSC capabilities were associated with reduced in-hospital mortality rates, and relevant aspects of care were found to be dependent on stroke type. 相似文献117.
A series of imidazolium salt derivatives was prepared as part of a search for subtype-selective antimuscarinic agents. On the basis of measurements of the antimuscarinic activity and subtype-selectivity for M2 and M3 muscarinic receptors, the structure-activity relationships of these compounds are discussed. 相似文献
118.
Kohki Yamamoto Toshifumi Suzuki Riyo Imamura Tetsuo Nagano Takayoshi Okabe Hiroyuki Miyachi 《Bioorganic & medicinal chemistry letters》2017,27(11):2567-2570
We present a practical synthesis of both enantiomers of 1,2,3,4-tetrahydroisoquinoline derivative IPPAM-1 (1), which is a positive allosteric modulator (PAM) of prostacyclin receptor (IP) and a candidate for treatment of pulmonary arterial hypertension without the side effects caused by IP agonists. Assay of cAMP production by CHO-K1 cells stably expressing human IP clearly demonstrated that the IPPAM activity resides exclusively on the R-form of 1. 相似文献
119.
We determined the effect of alpha-adrenergic blocking agent doxazosin on insulin resistance in 19 hypertensive patients (blood pressure [BP] >160/90 mmHg) with obesity (mean body mass index [BMI]: 26.7 +/- 1.9 kg/m (2)). Patients received doxazosin 4 mg/day for 12 months. Systolic and diastolic BP decreased from 169 +/- 10.8 mmHg to 147 +/- 11.9 mmHg (p < 0.0001) and from 102 +/- 8.1 mmHg to 87 +/- 5.0 mmHg (p < 0.0001), respectively. Insulin resistance and fasting immunoreactive insulin (IRI) were lower at study end vs. baseline (HOMA-R = 1.29 +/- 0.38 vs. 3.58 +/- 2.23 [p = 0.022]; IRI = 6.00 +/- 1.88 microU/ml vs 13.74 +/- 8.51 microU/ml [p = 0.046]). Total cholesterol was significantly reduced following treatment. Circulating TNF-alpha and leptin levels decreased significantly within 3 months of treatment; leptin was independently associated with insulin resistance when adjusted for BMI. We conclude that doxazosin improves insulin resistance and improves dyslipidemia in obese hypertensive patients, and has a beneficial effect on adipose endocrine activity. 相似文献
120.
Three bacterial strains, identified as Alcaligenes sp. strain D-59 and Pseudomonas sp. strains D-87 and D-186, capable of growing on 2,6-dimethylnaphthalene (2,6-DMN) as the sole source of carbon and energy were isolated from soil samples. 2,6-Naphthalene dicarboxylic acid was formed in the culture broths of these three strains grown on 2,6-DMN. In addition, 2-hydroxymethyl-6-methylnaphthalene and 6-methylnaphthalene-2-carboxylic acid were detected in the culture broth of strain D-87. Strain D-87 grew well on 1,2-, 1,3-, 1,4-, 1,5-, 2,3-, and 2,7-DMN as the sole source of carbon and energy and accumulated 2-methylnaphthalene-3-carboxylic acid and 2,3-naphthalene dicarboxylic acid from 2,3-DMN, 4-methylnaphthalene-1-carboxylic acid from 1,4-DMN, and 7-methylnaphthalene-2-carboxylic acid from 2,7-DMN. 相似文献