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21.
N Cho Y Nara M Harada T Sugo Y Masuda A Abe K Kusumoto Y Itoh T Ohtaki T Watanabe S Furuya 《Canadian Metallurgical Quarterly》1998,46(11):1724-1737
On the basis of structural information for the cyclic hexapeptide endothelin (ET) receptor antagonist, TAK-044, a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives bearing a carboxyl group and aromatic rings that were important for receptor binding were designed, synthesized, and evaluated for ET receptor binding affinities and inhibitory activities against ET-induced vasoconstriction. Optimization of each substituent in the thieno[2,3-d]pyrimidine ring led to the discovery of a novel and potent nonpeptide ET receptor antagonist, 6-(4-methoxymethoxyphenyl)-5-methylsulfonylaminomethyl-1-(2- methylthiobenzyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]p yrimidine-3- acetic acid (32 g), which binded to human ETA and ETB receptor subtypes with affinities (IC50) of 7.6 and 100 nM, respectively. Compound 32 g effectively antagonized ET-induced vasoconstriction and the inhibitory effect mediated by the ETB receptor was more potent than that of bosentan, while the inhibitory effect mediated by the ETA receptor was slightly less potent than that of bosentan. 相似文献
22.
A large public service organization was concerned with protection of its customers against hazards associated with furniture tipping in public use concourses. Because no injury experience was available for analysis, hazard patterns for tipping accidents were developed from an observational study of public interaction with the furniture. For each hazard pattern, anthropometric models were used to find the probability of the furniture being safe from tipping, for different age and gender combinations. A safety criterion was developed from this modeling, and used to change the weights of some furniture items to resist tipping. These modifications have now been implemented and are in widespread use. Implications for broader application of these models to the development of valid tipping standards for furniture are discussed. 相似文献
23.
S Kudoh I Komuro Y Hiroi Y Zou K Harada T Sugaya N Takekoshi K Murakami T Kadowaki Y Yazaki 《Canadian Metallurgical Quarterly》1998,273(37):24037-24043
Many lines of evidence have suggested that angiotensin II (AngII) plays an important role in the development of cardiac hypertrophy through AngII type 1 receptor (AT1). To determine whether AngII is indispensable for the development of mechanical stress-induced cardiac hypertrophy, we examined the activity of mitogen-activated protein kinase (MAPK) family and the expression of the c-fos gene as hypertrophic responses after stretching cultured cardiac myocytes of AT1a knockout (KO) mice. When cardiac myocytes were stretched by 20% for 10 min, extracellular signal-regulated protein kinases (ERKs) were strongly activated in KO cardiomyocytes as well as wild type (WT) myocytes. Both basal and stimulated levels of ERKs were higher in cardiomyocytes of KO mice than in those of WT mice. Activation of another member of the MAPK family, p38(MAPK), and expression of the c-fos gene were also induced by stretching cardiac myocytes of both types of mice. An AT1 antagonist attenuated stretch-induced activation of ERKs in WT cardiomyocytes but not in KO cardiomyocytes. Down-regulation of protein kinase C inhibited stretch-induced ERK activation in WT cardiomyocytes, whereas a broad spectrum tyrosine kinase inhibitor (genistein) and selective inhibitors of epidermal growth factor receptor (tyrphostin, AG1478, and B42) suppressed stretch-induced activation of ERKs in KO cardiac myocytes. Epidermal growth factor receptor was phosphorylated at tyrosine residues by stretching cardiac myocytes of KO mice. These results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation. 相似文献
24.
K Shinno S Ueda M Uno K Nishitani S Nagahiro M Harada 《Canadian Metallurgical Quarterly》1998,38(9):557-561
OBJECTIVE: Epidemiological evidence suggests that resistance to insulin is the common nexus of the accumulation of factors in patients at high cardiovascular risk. To find a test which enables resistance to insulin to be identified in large populations will allow preventive and therapeutic measures to be taken. DESIGN: Crossover. SETTING: Carrascosa del Campo and Cuenca Health Centres. PARTICIPANTS: 408 patients (154 men and 254 women), all the non-diabetic obese patients at the two health centres, were studied. MEASUREMENTS AND MAIN RESULTS: Levels of cholesterol, triglycerides and uric acid were measured. Patients were medically examined, and blood pressure, waist and hip measurements, toxic habits and cardiovascular history were found. They were classified by pathology and normograms. The O'Sullivan and microalbuminuria tests were performed, and all the statistical associations with biochemical and medical characteristics were studied. The O'Sullivan test was significantly associated (p < 0.01) with cardiovascular risk and insulin-resistance factors such as hypercholesterolaemia (RR 1.63), hypertension (RR 1.92), hypertriglyceridaemia (RR 2.47), hyperuricaemia (RR 1.80), with the Berglund resistance index (RR 1.52) and the microalbuminuria test (RR 1.83). The association was more consistent when there were a number of factors combining. There was no relationship with the waist/hip index found. CONCLUSION: The O'Sullivan test, on its own or with the microalbuminuria test, seems very useful for identifying obese subjects with resistance to insulin. 相似文献
25.
T Iwao A Toyonaga H Harada K Harada S Ban M Ikegami K Tanikawa 《Canadian Metallurgical Quarterly》1994,40(3):277-280
We studied oxygen saturation (SaO2) using a pulse oximeter in 120 patients undergoing non-sedated diagnostic upper gastrointestinal endoscopy. The baseline SaO2 was 98.3 +/- 1.0%. During the procedure, absence of oxygen desaturation (SaO2 > or = 95%) was found in 56%, mild oxygen desaturation (95% > SaO2 > or = 90%) in 35%, and severe oxygen desaturation (SaO2 < 90%) in 9%. Age (p = 0.56), gender (p = 0.47), smoking (p = 0.35), hemoglobin level (p = 0.52), body mass index (p = 0.27), or total endoscopy time (p = 0.72) was not related to the degree of oxygen desaturation. These results suggest that oxygen desaturation is frequently observed during non-sedated diagnostic upper gastrointestinal endoscopy although severe oxygen desaturation, which may induce rare but serious cardiopulmonary events, is not common. Furthermore, we cannot predict in which patients desaturation will occur. We therefore recommend continuous monitoring of arterial oxygenation in all patients during the procedure. 相似文献
26.
27.
A WC-Co coating was sprayed by the high-velocity oxyfuel process using a feedstock of tungsten carbide clad with cobalt. The
structure of the sprayed coating was characterized by x-ray diffraction (XRD), differential scanning calorimetry (DSC), and
differential thermal analysis (DTA). It was found that an amorphous phase of Co-W-C ternary alloy observed as a large, broad
peak in the XRD pattern can be formed in the as-sprayed WC-Co coating. The DSC, DTA, and XRD analyses revealed that the amorphous
phase crystallized at a temperature of around 873 K to metallic cobalt, Co6W6C, and tungsten with appreciable precipitation of free carbon. The heat treatment of as-sprayed WC-Co coating at a high temperature
of 1173 K suggests that annealing at a temperature higher than about 1104 K will promote the reaction of tungsten and cobalt
with carbon to form the complex carbide C06W6C. 相似文献
28.
Tsutomu Osawa Masashi Ando Saori Sakai Tadao Harada Osamu Takayasu 《Catalysis Letters》2005,105(1-2):41-45
The role of acetic acid added to the reaction media for the enantio-differentiating hydrogenation of methyl acetoacetate over
a (R,R)-tartaric acid-in-situ-modified nickel catalyst was studied from the viewpoint of the hydrogenation rate during repeated
runs. The hydrogenation of methyl acetoacetate on the “enantio-differentiating sites” of a tartaric acid-modified nickel catalyst
was specifically accelerated by the acetic acid added to the reaction media to increase the enantio-differentiating ability
of the catalyst. In order to increase the enantio-differentiating ability, the addition of acetic acid to the reaction media
was required in each run during the repeated use of the catalyst. 相似文献
29.
Attempts were carried out to enhance the surface hydrophilicity of poly(L ‐lactide), that is, poly(L ‐lactic acid) (PLLA) film, utilizing enzymatic, alkaline, and autocatalytic hydrolyses in a proteinase K/Tris–HCL buffered solution system (37°C), in a 0.01N NaOH solution (37°C), and in a phosphate‐buffered solution (100°C), respectively. Moreover, its chain‐scission mechanisms in these different media were studied. The advancing contact‐angle (θa) value of the amorphous‐made PLLA film decreased monotonically with the hydrolysis time from 100° to 75° and 80° without a significant molecular weight decrease, when enzymatic and alkaline hydrolyses were continued for 60 min and 8 h, respectively. In contrast, a negligible change in the θa value was observed for the PLLA films even after the autocatalytic hydrolysis was continured for 16 h, when their bulk Mn decreased from 1.2 × 105 to 2.2 × 104 g mol?1 or the number of hydrophilic terminal groups per unit weight increased from 1.7 × 10?5 to 9.1 × 10?5 mol g?1. These findings, together with the result of gravimetry, revealed that the enzymatic and alkaline hydrolyses are powerful enough to enhance the practical surface hydrophilicity of the PLLA films because of their surface‐erosion mechanisms and that its practical surface hydrophilicity is controllable by varying the hydrolysis time. Moreover, autocatalytic hydrolysis is inappropriate to enhance the surface hydrophilicity, because of its bulk‐erosion mechanism. Alkaline hydrolysis is the best to enhance the hydrophilicity of the PLLA films without hydrolysis of the film cores, while the enzymatic hydrolysis is appropriate and inappropriate to enhance the surface hydrophilicity of bulky and thin PLLA materials, respectively, because a significant weight loss occurs before saturation of θa value. The changes in the weight loss and θa values during hydrolysis showed that exo chain scission as well as endo chain scission occurs in the presence of proteinase K, while in the alkaline and phosphate‐buffered solutions, hydrolysis proceeds via endo chain scission. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1628–1633, 2003 相似文献
30.
Poly(l-lactide) (i.e. poly(l-lactic acid) (PLLA)) and poly(d-lactide) (i.e. poly(d-lactic acid) (PDLA)) and their equimolar enantiomeric blend (PLLA/PDLA) films were prepared and the effects of enantiomeric polymer blending on the thermal stability and degradation of the films were investigated isothermally and non-isothermally under nitrogen gas using thermogravimetry (TG). The enantiomeric polymer blending was found to successfully enhance the thermal stability of the PLLA/PDLA film compared with those of the pure PLLA and PDLA films. The activation energies for thermal degradation (ΔEtd) were evaluated at different weight loss values from TG data using the procedure recommended by MacCallum et al. The ΔEtd values of the PLLA/PDLA, PLLA, and PDLA films were in the range of 205-297, 77-132, and 155-242 kJ mol−1 when they were evaluated at weight loss values of 25-90% and the ΔEtd value of the PLLA/PDLA film was higher by 82-110 kJ mol−1 than the averaged ΔEtd value of the PLLA and PDLA films. The mechanism for the enhanced thermal stability of the PLLA/PDLA film is discussed. 相似文献