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121.
122.
Jose B Oniki Y Kato T Nishino N Sumida Y Yoshida M 《Bioorganic & medicinal chemistry letters》2004,14(21):5343-5346
Cyclic tetrapeptides containing trifluoromethyl and pentafluoroethyl ketone as zinc binding functional group were synthesized as potent HDAC inhibitors. Evaluation by human HDAC inhibition assay and p21 promoter assay showed that these inhibitors are promising anticancer agents. 相似文献
123.
Oishi K Honda S Takamura N Kusano Y Abe Y Moji K Takemoto T Tahara Y Aoyagi K 《Journal of PHYSIOLOGICAL ANTHROPOLOGY and Applied Human Science》2004,23(5):155-161
Body sizes at birth are important clinical indicators widely used for evaluation of prenatal growth. Japan had significant socioeconomic improvement around the 1960s, and these environmental changes may influence physiologically prenatal growth. Furthermore, in Japan, measurements of size at birth for birth certificates are weight and height. Thus, we can refer to annual data on weight and height, but not on head and chest circumference at birth. In this study we measured the weight, height, and head and chest circumference at birth among 6,563 Japanese singleton healthy infants, annually in 1962 and 1988, and examined secular trends of these anthropometric measurements. The boys consistently exceeded the girls in all four variables. Birth weight and height increased significantly from the 1960s to '70s, but did not differ between the '70s and '80s in both boys and girls. Secular trends of head and chest circumference were different from them. In both boys and girls, head and chest circumference increased significantly from the '60s to the '70s, but decreased significantly from the '70s to the '80s. No difference of head circumference during the '60s and '80s was found, but the difference of chest circumference was found. Size at birth was likely to increase from the '60s to '70s in Japan. These findings suggest that the environmental changes such as socioeconomic improvements influence the prenatal growth. 相似文献
124.
Yusuke?YamanoueEmail author Masaki?Miya Keiichi?Matsuura Masaya?Katoh Harumi?Sakai Mutsumi?Nishida 《Ichthyological Research》2004,51(3):269-273
We determined the complete nucleotide sequences of the mitochondrial genomes for the three currently recognized species of ocean sunfish: Mola mola, Masturus lanceolatus, and Ranzania laevis (Tetraodontiformes: Molidae). Each genome contained the 37 genes as found in teleosts, with the typical gene order in teleosts. Bayesian, maximum-likelihood, and maximum-parsimony analyses were conducted with the data set comprising concatenated nucleotide sequences from 36 genes (excluding the ND6 gene) of three molids and four outgroups (three tetraodontiforms plus a caproid). The resultant trees supported monophyly of the Molidae and its intrarelationships ((Mola, Masturus), Ranzania), which were congruent with previous morphology-based hypotheses. 相似文献
125.
126.
Koji?HattoriEmail author Ken?Ikeuchi Yusuke?Morita Yoshinori?Takakura 《Arthritis research & therapy》2004,7(1):R38
Osteoarthritis (OA) is one of the most prevalent chronic conditions. The histological cartilage changes in OA include surface
erosion and irregularities, deep fissures, and alterations in the staining of the matrix. The reversibility of these chondral
alterations is still under debate. It is expected that clinical and basic science studies will provide the clinician with
new scientific information about the natural history and optimal treatment of OA at an early stage. However, a reliable method
for detecting microscopic changes in early OA has not yet been established. We have developed a novel system for evaluating
articular cartilage, in which the acoustic properties of the articular cartilage are measured by introducing an ultrasonic
probe into the knee joint under arthroscopy. The purpose of this study was to assess microscopic cartilage damage in OA by
using this cartilage evaluation system on collagenase-treated articular cartilage in vivo and in vitro. Ultrasonic echoes from articular cartilage were converted into a wavelet map by wavelet transformation. On the wavelet map,
the maximum magnitude and echo duration were selected as quantitative indices. Using these indices, the articular cartilage
was examined to elucidate the relationships of the ultrasonic analysis with biochemical, biomechanical and histological analyses.
In the in vitro study, the maximum magnitude decreased as the duration of collagenase digestion increased. Correlations were observed between
the maximum magnitude and the proteoglycan content from biochemical findings, and the maximum magnitude and the aggregate
modulus from biomechanical findings. From the histological findings, matrix staining of the surface layer to a depth of 500
μm was closely related to the maximum magnitude. In the in vivo study, the maximum magnitude decreased with increasing duration of the collagenase injection. There was a significant correlation
between the maximum magnitude and the aggregate modulus. The evaluation system therefore successfully detected microscopic
changes in degenerated cartilage with the use of collagen-induced OA. 相似文献
127.
Takamura M Sakurai M Yamada E Fujita S Yachi M Takagi T Isobe A Hagisawa Y Fujiwara T Yanagisawa H 《Bioorganic & medicinal chemistry》2004,12(9):2419-2439
We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having alpha-substituted-beta-phenylpropionic acids. In this series, we obtained potent PPAR alpha/gamma dual agonist (S)-9d, with which activation of PPAR alpha and PPAR gamma was considerably more potent than that of the reference compounds GW9578 22 and rosiglitazone 3, respectively. This means (S)-9d is of the strongest class of PPAR alpha/gamma dual agonists. In the course of this study, we also obtained 8h, which indicated potent plasma glucose lowering effect in spite of weak PPAR alpha/gamma agonistic activity. 相似文献
128.
129.
RalA activation at nascent lamellipodia of epidermal growth factor-stimulated Cos7 cells and migrating Madin-Darby canine kidney cells 下载免费PDF全文
RalA, a member of the Ras-family GTPases, regulates various cellular functions such as filopodia formation, endocytosis, and exocytosis. On epidermal growth factor (EGF) stimulation, activated Ras recruits guanine nucleotide exchange factors (GEFs) for RalA, followed by RalA activation. By using fluorescence resonance energy transfer-based probes for RalA activity, we found that the EGF-induced RalA activation in Cos7 cells was restricted at the EGF-induced nascent lamellipodia, whereas under a similar condition both Ras activation and Ras-dependent translocation of Ral GEFs occurred more diffusely at the plasma membrane. This EGF-induced RalA activation was not observed when lamellipodial protrusion was suppressed by a dominant negative mutant of Rac1, a GTPase-activating protein for Cdc42, inhibitors of phosphatidylinositol 3-kinase, or inhibitors of actin polymerization. On the other hand, EGF-induced lamellipodial protrusion was inhibited by microinjection of the RalA-binding domains of RalBP1 and Sec5. Furthermore, we found that RalA activity was high at the lamellipodia of migrating Madin-Darby canine kidney cells and that the migration of Madin-Darby canine kidney cells was perturbed by the microinjection of RalBP1-RalA-binding domain. Thus, RalA activation is required for the induction of lamellipodia, and conversely, lamellipodial protrusion seems to be required for the RalA activation, suggesting the presence of a positive feedback loop between RalA activation and lamellipodial protrusion. Our observation also demonstrates that the spatial regulation of RalA is conducted by a mechanism distinct from the temporal regulation conducted by Ras-dependent plasma membrane recruitment of Ral guanine nucleotide exchange factors. 相似文献
130.
Structural studies of [2',6'-dimethyl-L-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond 总被引:1,自引:0,他引:1
Okada Y Fujita Y Motoyama T Tsuda Y Yokoi T Li T Sasaki Y Ambo A Jinsmaa Y Bryant SD Lazarus LH 《Bioorganic & medicinal chemistry》2003,11(9):1983-1994
Analogues of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH(2)) (1) were designed to examine the importance of each residue on mu-opioid receptor interaction. Replacement of Tyr(1) by 2',6'-dimethyl-L-tyrosine (Dmt) (9-12) exerted profound effects: [Dmt(1)]EM-2 (9) elevated mu-opioid affinity 4.6-fold (K(i mu=0.15 nM) yet selectivity fell 330-fold as delta-affinity rose (K(i)delta=28.2 nM). This simultaneous increased mu- and delta-receptor bioactivities resulted in dual agonism (IC(50)=0.07 and 1.87 nM, respectively). While substitution of Phe(4) by a phenethyl group (4) decreased mu affinity (K(i)mu=13.3 nM), the same derivative containing Dmt (12) was comparable to EM-2 but also acquired weak delta antagonism (pA(2)=7.05). 1H NMR spectroscopy revealed a trans configuration (1:2 to 1:3, cis/trans) in the Tyr-Pro amide bond, but a cis configuration (5:3 to 13:7, cis/trans) with Dmt-Pro analogues. 相似文献