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111.
Hatsumi Yoshiki Matomo Nishio Yuji Ikegaya Naoya Takahashi Norio Matsuki Yasuhisa Fujibayashi Yoshiharu Yonekura Toshihiko Momiyama Ikunobu Muramatsu 《Journal of neurochemistry》2013,126(3):360-371
Muscarinic acetylcholine receptors (mAChRs) are well known to transmit extracellular cholinergic signals into the cytoplasm from their position on the cell surface. However, we show here that M1‐mAChRs are also highly expressed on intracellular membranes in neurons of the telencephalon and activate signaling cascades distinct from those of cell surface receptors, contributing uniquely to synaptic plasticity. Radioligand‐binding experiments with cell‐permeable and ‐impermeable ligands and immunohistochemical observations revealed intracellular and surface distributions of M1‐mAChRs in the hippocampus and cortex of rats, mice, and humans, in contrast to the selective occurrence on the cell surface in other tissues. All intracellular muscarinic‐binding sites were abolished in M1‐mAChR‐gene‐knockout mice. Activation of cell surface M1‐mAChRs in rat hippocampal neurons evoked phosphatidylinositol hydrolysis and network oscillations at theta rhythm, and transiently enhanced long‐term potentiation. On the other hand, activation of intracellular M1‐mAChRs phosphorylated extracellular‐regulated kinase 1/2 and gradually enhanced long‐term potentiation. Our data thus demonstrate that M1‐mAChRs function at both surface and intracellular sites in telencephalon neurons including the hippocampus, suggesting a new mode of cholinergic transmission in the central nervous system. 相似文献
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114.
Tomohiro Yamaguchi Youichi Suzuki Ryuichi Katakura Takusaburo Ebina Junkichi Yokoyama Yoshiaki Fujimiya 《Cancer immunology, immunotherapy : CII》1998,47(2):97-103
γδT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the
activation and proliferation of circulating γδT cells should be fully understood prior to their adoptive transfer to cancer
patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified γδT cells isolated from
glioblastoma patients. γδT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) αβγ, but the levels of IL-2Rβ
or γ expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal γδT
cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations
of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response,
this activity was completely or partially abrogated by anti-IL-2Rβ, or anti-IL-2Rγ antibodies, but not by anti-IL-2Rα antibodies.
Incubation of γδT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific
autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific
activity could be significantly blocked by anti-IL-2Rγ and anti-IL-2R-β mAb, but not by anti-IL-2Rα mAb. Thus, in contrast
to IL-2, IL-15 activates tumor-specific γδT cells through the components of IL-2Rβ and IL-2Rγ, but not IL-2Rα. These enhanced
in vitro tumor-specific and proliferative responses of γδT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic
use of γδT cells in cancer patients.
Received: 23 January 1998 / Accepted: 20 May 1998 相似文献
115.
Ishikawa Keiko; Kamada Hiroshi; Yamaguchi Isomaro; Takahashi Nobutaka; Harada Hiroshi 《Plant & cell physiology》1988,29(3):461-466
Carrot and tobacco plants were transformed with Agrobacteriumtumefaciens harboring wild-type, aux or cyt Tiplasmids. In tobacco, these wild and mutant Ti plasmids inducedthe formation of non-morphogenic galls, galls with shoots, andgalls with roots, respectively. In carrot, however, transformationwith any of these plasmids resulted in only the formation ofamorphous tumors. Determination of IAA and cytokinin contentsshowed that in tobacco, significantly high amounts of cytokininsor IAA are present in the cells transformed with Ti plasmidspossessing cytokinin or IAA biosynthetic genes, respectively.In carrot, cytokinin contents were also high in the cells transformedwith Ti plasmids having cytokinin biosynthetic genes, whereasIAA contents of the cells were similar regardless of the plasmidsused for transformation. These results suggest that the mechanism regulating IAA metabolismmay be different in tobacco and carrot. (Received June 25, 1987; Accepted February 1, 1988) 相似文献
116.
Hara Takayuki; Nagatani Akira; Yamaguchi Isomaro; Murofushi Noboru; Takahashi Nobutaka; Furuya Masaki 《Plant & cell physiology》1988,29(6):913-918
In the fern Lygodium japonicum, the effect of the exogenousapplication of two gibberellin methyl esters, gibberellin A4methyl ester (GA4Me) and gibberellin A20 methyl ester (GA20Me)on spore germination in the dark and uptake of GA4Me and GA20Meby spores was investigated. Tritiated GA4Me and GA20Me wereprepared and used as radioactive tracers. The activity of GA4Mewas more than 100-fold that of GA20Me for the induction of sporegermination. When treated for 24 h, the activity for inducingspore germination remained after removal of the gibberellinmethyl esters from the medium. The amount of GA4Me taken upby spores was more than three times that of GA20Me throughoutthe 24 h time course of treatment. The uptake of both gibberellinmethyl esters was proportional to the external concentrationfor the range of concentrations between 109 M and 106M. When treated with the tritiated gibberellin methyl estersat 106 M and 107 M for 24 h, most of the gibberellinmethyl esters taken up by the spores were not metabolized. Althoughthe uptake of the two gibberellin methyl esters differed by3- to 5- fold, their abilities to induce spore germination differedby more than 100-fold. Therefore, the difference in the activityof the two gibberellin methyl esters regarding the inductionof spore germination could not be explained solely by the differencein their uptake. (Received January 11, 1988; Accepted May 26, 1988) 相似文献
117.
E Benedikt A Gossauer H P K?st W Miki K Yamaguchi 《European journal of biochemistry》1988,175(3):643-648
The ovaries of the marine snail Turbo cornutus contain a number of pigments. So far, the presence of carotenoids and a chromoprotein with a bile pigment, called turboverdin (= 3(2)-hydroxy-mesobiliverdin IX alpha), as its prosthetic group are known. The present work describes the isolation and structure elucidation of two further bile pigments, biliverdin IX delta and neobiliverdin IX delta. This is the first report of naturally occurring bile pigments with IX delta structure. 相似文献
118.
The genomes of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) consist of single-stranded RNA encoding polyproteins, which are processed to individual functional proteins by virus-encoded specific proteases. These proteases have been used as targets for drug development. Here, instead of targeting these proteases to inhibit viral infection, we utilized the protease activity to activate a toxic protein to prevent viral infection. We engineered the MazE-MazF antitoxin-toxin system of Escherichia coli to fuse a C-terminal 41-residue fragment of antitoxin MazE to the N-terminal end of toxin MazF with a linker having a specific protease cleavage site for either HIV PR (HIV-1 protease), NS3 protease (HCV protease), or factor Xa. These fusion proteins formed a stable dimer (instead of the MazF(2)-MazE(2)-MazF(2) heterohexamer in nature) to inactivate the ACA (sequence)-specific mRNA interferase activity of MazF. When the fusion proteins were incubated with the corresponding proteases, the MazE fragment was cleaved from the fusion proteins, releasing active MazF, which then acted as an ACA-specific mRNA interferase cleaving single-stranded MS2 phage RNA. The intramolecular regulation of MazF toxicity by proteases as demonstrated may provide a novel approach for preventive and therapeutic treatments of infection by HIV-1, HCV, and other single-stranded RNA viruses. 相似文献
119.
Matsuki N Ichiba S Ishikawa T Nagano O Takeda M Ujike Y Yamaguchi T 《European biophysics journal : EBJ》2012,41(6):571-578
Microbubbles have been used in a variety of fields and have unique properties, for example shrinking collapse, long lifetime, efficient gas solubility, a negatively charged surface, and the ability to produce free radicals. In medicine, microbubbles have been used mainly as diagnostic aids to scan various organs of the body, and they have recently been investigated for use in drug and gene delivery. However, there have been no reports of blood oxygenation by use of oxygen microbubble fluids without shell reagents. In this study, we demonstrated that nano or microbubbles can achieve oxygen supersaturation of fluids, and may be sufficiently small and safe for infusion into blood vessels. Although Po(2) increases in fluids resulting from use of microbubbles were inhibited by polar solvents, normal saline solution (NSS) was little affected. Thus, NSS is suitable for production of oxygen-rich fluid. In addition, oxygen microbubble NSS effectively improved hypoxic conditions in blood. Thus, use of oxygen microbubble (nanobubble) fluids is a potentially effective novel method for oxygenation of hypoxic tissues, for infection control, and for anticancer treatment. 相似文献
120.
S Nagafuchi T Okeda M Nakamura K Yamaguchi J Ono R Takaki 《Endocrinologia japonica》1982,29(3):395-399
Anti-rat islet serum was prepared in guinea pigs by multiple subcutaneous inoculations of rat islets homogenates emulsified in complete Freund's adjuvant (CFA). The anti-rat islet serum was cytotoxic against rat spleen cells in the presence of complement and the nonspecific antibodies were observed with homogenates of rat livers and spleens. After absorption, the serum lost the cytotoxicity against the rat spleen cells yet showed specific cytotoxicity against the rat islet cells. The binding capacity of anti-rat islet antibody was determined by the indirect immunofluorescence test using FITC conjugated rabbit anti-guinea pig IgG serum. As the guinea pig anti-rat islet serum contained anti-insulin antibody, the role of this antibody in this cytotoxic activity and surface immunofluorescence was studied. However, the anti-insulin antibody used as the control showed neither cytotoxicity nor surface immunofluorescence. After neutralizing the anti-insulin antibody in the antiserum with insulin, the serum remained cytotoxic to the rat islet cells and a surface immunofluorescence appeared. These data show that specific anti-rat islet cell surface antibody can be produced in guinea pigs by multiple inoculations of rat islets homogenates with CFA. 相似文献