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排序方式: 共有579条查询结果,搜索用时 62 毫秒
51.
52.
Hori H Nagasawa H Ishibashi M Uto Y Hirata A Saijo K Ohkura K Kirk KL Uehara Y 《Bioorganic & medicinal chemistry》2002,10(10):3257-3265
A series of 2-hydroxyarylidene-4-cyclopentene-1,3-diones were designed, synthesized, and evaluated with respect to protein tyrosine kinase (PTK) inhibition, mitochondrial toxicity, and antitumor activity. Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyrphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17, a potent antitumor tyrphostin. The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties, including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to protein tyrosine kinase inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates that PTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AG17. 相似文献
53.
Osamu Katano Yoshimasa Aonuma Kei’ichiroh Iguchi Taiga Yodo Naoto Matsubara 《Ichthyological Research》2003,50(4):349-357
Response to predators may not be identical between different prey species with different life histories and body sizes, particularly when the threat of predation is not great. To clarify this hypothesis, we introduced two prey species (10 Japanese dace, Tribolodon hakonensis, and 10 pale chub, Zacco platypus) into each experimental pond (in total, 8 ponds×4 trials) in which benthic algae had been allowed to grow. The presence or absence of Far Eastern catfish, Silurus asotus, and a refuge for prey fish was used to produce four treatments. The presence of catfish and/or a refuge did not affect either the feeding behavior or growth rate of Japanese dace. In contrast, when catfish were present and no refuge was available, the incidence of bottom feeding for pale chub greatly decreased. Pale chub growth rate was low when catfish were present and a refuge was available, indicating that pale chub spent more of their time in the refuge and lost opportunities of acquiring food. Japanese dace can reach a threshold size at which the prey are safe from predation, but pale chub cannot, and this may explain the differences in response to predators of the two species. 相似文献
54.
Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice 总被引:19,自引:0,他引:19
Okazaki T Tanaka Y Nishio R Mitsuiye T Mizoguchi A Wang J Ishida M Hiai H Matsumori A Minato N Honjo T 《Nature medicine》2003,9(12):1477-1483
We recently reported that mice deficient in the programmed cell death-1 (PD-1) immunoinhibitory coreceptor develop autoimmune dilated cardiomyopathy (DCM), with production of high-titer autoantibodies against a heart-specific, 30-kDa protein. In this study, we purified the 30-kDa protein from heart extract and identified it as cardiac troponin I (cTnI), encoded by a gene in which mutations can cause familial hypertrophic cardiomyopathy (HCM). Administration of monoclonal antibodies to cTnI induced dilatation and dysfunction of hearts in wild-type mice. Monoclonal antibodies to cTnI stained the surface of cardiomyocytes and augmented the voltage-dependent L-type Ca2+ current of normal cardiomyocytes. These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes. 相似文献
55.
Han SY Inoue H Terada T Kamoda S Saburi Y Sekimata K Saito T Kobayashi M Shinozaki K Yoshida S Asami T 《Journal of enzyme inhibition and medicinal chemistry》2003,18(3):279-283
Lignostilbene-alpha,beta-dioxygenase (LSD, EC 1.13.11.43) is involved in oxidative cleavage of the central double bond of lignostilbene to form the corresponding aldehydes by a mechanism similar to those of 9-cis-epoxycarotenoid dioxygenase and beta-carotene 15,15'-dioxygenase, key enzymes in abscisic acid biosynthesis and vitamin A biosynthesis, respectively. In this study, several N-benzylideneanilines and amine were synthesized and examined for their efficacy as inhibitors of LSD. N-(4-Hydroxybenzylidene)-3-methoxyaniline was found to be a potent inhibitor with IC50 = 0.3 microM and N-(4-hydroxybenzyl)-3-methoxyaniline was also active with IC50 = 10 microM. The information obtained from the structure-activity relationships study here can aid in discovering inhibitors of both abscisic acid and vitamin A biosynthesis. 相似文献
56.
NRSF regulates the fetal cardiac gene program and maintains normal cardiac structure and function 总被引:1,自引:0,他引:1
57.
Miho Iijima Kazuhiro Aiba Yoshimasa Tanaka Hideko Urushihara 《Journal of plant research》1998,111(1):93-96
Two cDNA fragments induced in developing zygotes ofDictyostelium discoideum were isolated by mRNA differential display. the relevant genes were also found to be expressed during asexual development,
suggesting that sexual and asexual development share common molecular mechanisms inD. discoideum. 相似文献
58.
Fujito Kageyama Yoshimasa Kobayashi Gou Murohisa Erina Shimizu Fumitaka Suzuki Masataka Kikuyama Kenichi Souda Tsunehisa Kawasaki Hirotoshi Nakamura 《Biological trace element research》1998,64(1-3):185-196
Recent reports suggest the hepatic iron concentration (HIC) may influence the activity of hepatitis and the response to interferon
(IFN) therapy in patients with chronic hepatitis C (CH-C). We have evaluated iron status in 28 patients with CH-C and determined
if pretreatment iron status can predict the response to IFN-α therapy in these patients. Increased serum iron, transferrin
saturation, and ferritin levels were observed in 3 (11%), 11 (39%), and 5 (18%) patients, respectively. Hepatic iron deposits
were histologically detected in 17 (61%) patients, and 14 of them had stainable hepatocytic iron. However, all HIC values
were within the normal range (203–1279 μg/g). Seven of 17 patients treated with IFN-α for 6 mo had normalization of serum
transaminases and disappearance of serum HCV-RNA (responders). Nonresponders had a significantly higher median HIC compared
with responders (710 vs 343 μg/g, respectively;p < 0.05). There was no significant difference in other pretreatment iron parameters, serum HCV-RNA level, or HCV-genotype between
responders and nonresponders. In conclusion, mild hepatic iron accumulation occurs in patients with CH-C. Increased hepatic
iron stores are associated with poor response to IFN therapy. Pretreatment HIC may be an additional host-specific parameter
with a predictive value for responsiveness to IFN therapy, in addition to well-known predictive viral factors. 相似文献
59.
Yoshimasa Takizawa Yong Qing Motoki Takaku Takako Ishida Yuichi Morozumi Takashi Tsujita Toshiaki Kogame Kouji Hirota Masayuki Takahashi Takehiko Shibata Hitoshi Kurumizaka Shunichi Takeda 《Nucleic acids research》2010,38(15):5059-5074
RAD51 is a key factor in homologous recombination (HR) and plays an essential role in cellular proliferation by repairing DNA damage during replication. The assembly of RAD51 at DNA damage is strictly controlled by RAD51 mediators, including BRCA1 and BRCA2. We found that human RAD51 directly binds GEMIN2/SIP1, a protein involved in spliceosome biogenesis. Biochemical analyses indicated that GEMIN2 enhances the RAD51–DNA complex formation by inhibiting RAD51 dissociation from DNA, and thereby stimulates RAD51-mediated homologous pairing. GEMIN2 also enhanced the RAD51-mediated strand exchange, when RPA was pre-bound to ssDNA before the addition of RAD51. To analyze the function of GEMIN2, we depleted GEMIN2 in the chicken DT40 line and in human cells. The loss of GEMIN2 reduced HR efficiency and resulted in a significant decrease in the number of RAD51 subnuclear foci, as observed in cells deficient in BRCA1 and BRCA2. These observations and our biochemical analyses reveal that GEMIN2 regulates HR as a novel RAD51 mediator. 相似文献
60.
Nakazawa Y Sagane Y Kikuchi T Uchino M Nagai T Sato H Toeda K Takano K 《The protein journal》2010,29(8):598-608
We previously isolated Streptomyces racemochromogenes strain 10-3, which produces a phospholipase D (PLD) with high transphosphatidylation activity. Here, we purified and cloned
the PLD (PLD103) from the strain. PLD103 exerted the highest hydrolytic activity at a slightly alkaline pH, which is in contrast
to the majority of known Streptomyces PLDs that have a slightly acidic optimum pH. PLD103 shares only 71–76% amino acid sequence identity with other Streptomyces PLDs that have a slightly acidic optimum pH; thus, the diversity in the primary structure might explain the discrepancy observed
in the optimum pH. The purified PLD displayed high transphosphatidylation activity in the presence of glycerol, l-serine, and 2-aminoethanol hydrochloride with a conversion rate of 82–97% in a simple one-phase system, which was comparable
to the rate of other Streptomyces PLDs in a complicated biphasic system. 相似文献