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排序方式: 共有181条查询结果,搜索用时 15 毫秒
21.
Kurata H Kusumi K Otsuki K Suzuki R Kurono M Tokuda N Takada Y Shioya H Mizuno H Komiya T Ono T Hagiya H Minami M Nakade S Habashita H 《Bioorganic & medicinal chemistry letters》2012,22(1):144-148
Structure-activity relationship (SAR) of sphingosine-1-phosphate receptor agonists with a dihydronaphthalene scaffold was investigated. Compound 1 was modified to improve S1P(1) agonistic activity and in vivo peripheral lymphocyte lowering (PLL) activity without impairing selectivity over S1P(3) agonistic activity. A detailed SAR study of the terminal lipophilic part revealed that the introduction of substituents on the propylene linker and the terminal benzene ring influences in vitro and PLL activities. Compound 6n bearing a (S)-methyl group at the 2-position on the propylene linker and chlorine at the para-position on the terminal benzene ring showed potent hS1P(1) agonistic activity with excellent selectivity over hS1P(3) and in vivo PLL activity in mice. 相似文献
22.
23.
Takahashi H Amagai M Nishikawa T Fujii Y Kawakami Y Kuwana M 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(2):1526-1535
Autoreactive T cells are thought to be involved in the pathogenesis of autoimmune diseases, but evidence for their direct pathogenicity is almost lacking. Herein we established a unique system for evaluating the in vivo pathogenicity of desmoglein 3 (Dsg3)-reactive T cells at a clonal level in a mouse model for pemphigus vulgaris (PV), an autoimmune blistering disease induced by anti-Dsg3 autoantibodies. Dsg3-reactive CD4(+) T cell lines generated in vitro were adoptively transferred into Rag-2(-/-) mice with primed B cells derived from Dsg3-immunized Dsg3(-/-) mice. Seven of 20 T cell lines induced IgG anti-Dsg3 Ab production and acantholytic blister, a typical disease phenotype, in recipient mice. Comparison of the characteristics between pathogenic and nonpathogenic Dsg3-reactive T cell lines led to the identification of IL-4 and IL-10 as potential factors associated with pathogenicity. Further in vitro analysis showed that IL-4, but not IL-10, promoted IgG anti-Dsg3 Ab production by primed B cells. Additionally, adenoviral expression of soluble IL-4Ralpha in vivo suppressed IgG anti-Dsg3 Ab production and the PV phenotype, indicating a pathogenic role of IL-4. This strategy is useful for evaluating the effector function of autoreactive T cells involved in the pathogenesis of various autoimmune diseases. 相似文献
24.
We investigated the effect of magnesium supplementation on zinc distribution in rats given excess calcium as carbonate. Rats
were given a control diet (5 g/kg calcium and 0.5 g/kg magnesium), a high calcium diet (HC, 25 g/kg calcium and 0.5 g/kg magnesium)
or the high calcium diet supplied with magnesium (HCM, 25 g/kg calcium and 2.5 g/kg magnesium) for 4 weeks. Calcium carbonate
and magnesium oxide were used for increasing these mineral concentrations in diets. Although feed intake did not differ among
the groups, the excess calcium suppressed feed efficiency, irrespective of dietary magnesium concentration. Femoral magnesium
concentration was lower in the HC group than in the control and the HCM groups. Femoral zinc concentration was higher in the
HC group and the HCM group than in the control group. The zinc concentration in the kidney was lower in the HC group and the
HCM group than in the control group. The excess calcium did not affect zinc concentration in plasma and other tissues such
as the liver, testis, and spleen, irrespective of dietary magnesium. These results suggest that the increasing bone zinc and
the decreasing renal zinc do not result from magnesium insufficiency in rats given excess calcium as carbonate. 相似文献
25.
Hatano M Sasaki S Ohata S Shiratsuchi Y Yamazaki T Nagata K Kobayashi Y 《Cellular immunology》2008,251(1):25-30
TNF-α, IFN-γ, IL-4, and MIP-2 are known to be involved in Con A-induced hepatitis. Although Kupffer cells are reportedly involved in TNF-α production, it is largely unknown whether or not Kupffer cells also play a role in the production of other cytokines, such as IFN-γ, IL-4, and MIP-2. In this study we examined the liver injury and the levels of plasma cytokines, including above four cytokines, KC, and IL-10 in Kupffer cell-depleted mice obtained through administration of liposome-encapsulated dichloromethylene bisphosphonate. The liver injury was significantly suppressed in Kupffer cell-depleted mice, as assessed as to the plasma ALT level and histochemistry. The cytokine levels were also significantly suppressed in such mice except for those of IFN-γ, which was slightly suppressed at 12 h, and IL-10, which was not significantly suppressed at any time. Apoptosis was also significantly suppressed in such mice, as found immunohistochemically with anti-ssDNA Ab. Taken together, these results suggest that Kupffer cells are involved in the production of MIP-2, KC, IL-4, and TNF-α in Con A-induced hepatitis, thereby contributing to the liver injury either directly or indirectly. 相似文献
26.
Daiju Kitagawa Shuhei Tanemura Shinya Ohata Nao Shimizu Jungwon Seo Gen Nishitai Tomomi Watanabe Kentaro Nakagawa Hiroyuki Kishimoto Teiji Wada Tohru Tezuka Tadashi Yamamoto Hiroshi Nishina Toshiaki Katada 《The Journal of biological chemistry》2002,277(1):366-371
Ultraviolet (UV) irradiation stimulates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), which is a member of the mitogen-activated protein kinase (MAPK) superfamily and implicated in stress-induced apoptosis. UV also induces the activation of another MAPK member, extracellular signal-regulated kinase (ERK), which is typically involved in a growth-signaling cascade. However, the UV-induced signaling pathway leading to ERK activation, together with the physiological role, has remained unknown. Here we examined the molecular mechanism and physiological function of UV-induced ERK activation in human epidermoid carcinoma A431 cells that retain a high number of epidermal growth factor (EGF) receptors. UV-induced ERK activation was accompanied with the Tyr phosphorylation of EGF receptors, and both responses were completely abolished in the presence of a selective EGF receptor inhibitor (AG1478) or the Src inhibitor PP2 and by the expression of a kinase-dead Src mutant. On the other hand, SAPK/JNK activation by UV was partially inhibited by these inhibitors. UV stimulated Src activity in a manner similar to the ERK activation, but the Src activation was insensitive to AG1478. UV-induced cell apoptosis measured by DNA fragmentation and caspase 3 activation was enhanced by AG1478 and an ERK kinase inhibitor (U0126) but inhibited by EGF receptor stimulation by the agonist. These results indicate that UV-induced ERK activation, which provides a survival signal against stress-induced apoptosis, is mediated through Src-dependent Tyr phosphorylation of EGF receptors. 相似文献
27.
We investigated the effects of estradiol-treated females on the behavior of male budgerigars. In comparison to control females,
females given implants of estradiol showed elevated nest behavior and darker cere color, which are characteristics of breeding
females. After we confirmed the efficacy of estradiol treatment on behavior and morphology, each female was paired with a
male mate. Males paired with estradiol-treated females showed more courtship behavior (auditory and visual display, and courtship
feeding) to their mates than males paired with control females. These data indicate that budgerigar females with a high estrogen
level enhance males' courtship behavior. Since males did not show response to estradiol-treated females soon after females
were introduced, effects of estradiol-treated female budgerigars may be mediated by the endocrine system, rather than wholly
by the nervous system, of males.
Electronic Publication 相似文献
28.
Administration of 4-8 mg testosterone propionate significantly raised 25-hydroxycalciferol levels in the ultraviolet irradiated rats compared to the ultraviolet irradiated controls, but failed to influence serum 25-hydroxycalciferol levels in the non-irradiated animals. Estradiol benzoate and progesterone did not influence serum 25-hydroxycalciferol levels regardless of the ultraviolet irradiation. These findings implicate that testosterone enhances vitamin D biosynthesis induced by ultraviolet irradiation in rats, in accordance with the clinical observation that males often show higher levels of serum 25-hydroxycalciferol than females. 相似文献
29.
Nitrite, a stable metabolite of nitric oxide (NO), is measured fluorometrically as an indicator of NO production using 2,3-diaminonaphthalene. In cultured cells, it has been believed that a longer period of incubation improves the detection sensitivity because of the accumulation of nitrite formed from NO in culture media. However, here we show that nitrite formed from nitrogen oxide air pollutants accumulates continuously in culture media during the incubation and interferes with the measurement of NO as nitrite. Thus, a proper period of incubation is important to allow maximum nitrite signals from NO with minimum background nitrite from the air. 相似文献
30.
Takeji Mizunuma 《Bioscience, biotechnology, and biochemistry》2013,77(6):491-502
This report is concerned with the time course of changes of several enzymes during endogenous respiration. It was observed that enzymes such as deaminases, amidases and transaminases found in the mycelia increased in activity more or less during endogenous respiration. It was assumed that enzyme formation occurred as the result of glucose starvation or depression of carbohydrate metabolism during endogenous respiration of the mold mycelia on buffer solution. 相似文献