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181.
AimsThere is an urgent need for positron emission tomography (PET) imaging of the nicotinic acetylcholine receptors (nAChR) to study the role of the nicotinic system in Alzheimer's and Parkinson's diseases, schizophrenia, drug dependence and many other disorders. Greater understanding of the underlying mechanisms of the nicotinic system could direct the development of medications to treat these disorders. Central nAChRs also contribute to a variety of brain functions, including cognition, behavior and memory.Main methodsCurrently, only two radiotracers, (S)-3-(azetidin-2-ylmethoxy)-2-[18F]fluoropyridine (2-[18F]FA) and (S)-5-(azetidin-2-ylmethoxy)-2-[18F]fluoropyridine (6-[18F]FA), are available for studying nAChRs in human brain using PET. However, the “slow” brain kinetics of these radiotracers hamper mathematical modeling and reliable measurement of kinetic parameters since it takes 4–7 h of PET scanning for the tracers to reach steady state. The imaging drawbacks of the presently available nAChR radioligands have initiated the development of radioligands with faster brain kinetics by several research groups.Key findingsThis minireview attempts to survey the important achievements of several research groups in the discovery of PET nicotinic radioligands reached recently. Specifically, this article reviews papers published from 2006 through 2008 describing the development of fifteen new nAChR 11C-and 18F-ligands that show improved imaging properties over 2-[18F]FA.SignificanceThe continuous efforts of radiomedicinal chemists led to the development of several interesting PET radioligands for imaging of nAChR including [18F]AZAN, a potentially superior alternative to 2-[18F]FA. 相似文献
182.
Glucose regulated proteins 78 and 75 bind to the receptor for hyaluronan mediated motility in interphase microtubules 总被引:3,自引:0,他引:3
Kuwabara H Yoneda M Hayasaki H Nakamura T Mori H 《Biochemical and biophysical research communications》2006,339(3):971-976
The receptor for hyaluronan mediated motility (RHAMM), which is a hyaluronan-binding protein, is a centrosomal and microtubal protein. Here, we have identified two RHAMM-binding proteins, glucose regulated protein (GRP) 78 and GRP75, using co-immunoprecipitation analysis. These two proteins directly bound to glutathione-S-transferase-RHAMM fusion proteins. By double immunostaining, GRP78 and GRP75 colocalized with RHAMM in interphase microtubules, but were separated in mitotic spindles. Prevention of microtubule polymerization by TN-16 and vincristine sulfate induced RHAMM overexpression without a significant change in GRP78/75. Taken together, GRP78/75 and RHAMM complexes may stabilize microtubules in the interphase, associated with a downregulation of RHAMM. These results reveal a new biochemical activity of RHAMM. 相似文献
183.
Watanabe Y Inanami O Horiuchi M Hiraoka W Shimoyama Y Inagaki F Kuwabara M 《Biochemical and biophysical research communications》2006,350(3):549-556
We analyzed the pH-induced mobility changes in moPrP(C) alpha-helix and beta-sheets by cysteine-scanning site-directed spin labeling (SDSL) with ESR. Nine amino acid residues of alpha-helix1 (H1, codon 143-151), four amino acid residues of beta-sheet1 (S1, codon 127-130), and four amino acid residues of beta-sheet2 (S2, codon 160-163) were substituted for by cysteine residues. These recombinant mouse PrP(C) (moPrP(C)) mutants were reacted with a methane thiosulfonate sulfhydryl-specific spin labeling reagent (MTSSL). The 1/deltaH of the central (14N hyperfine) component (M(I) = 0) in the ESR spectrum of spin-labeled moPrP(C) was measured as a mobility parameter of nitroxide residues (R1). The mobilities of E145R1 and Y149R1 at pH 7.4, which was identified as a tertiary contact site by a previous NMR study of moPrP, were lower than those of D143R1, R147R1, and R150R1 reported on the helix surface. Thus, the mobility in the H1 region in the neutral solution was observed with the periodicity associated with a helical structure. On the other hand, the values in the S2 region, known to be located in the buried side, were lower than those in the S1 region located in the surface side. These results indicated that the mobility parameter of the nitroxide label was well correlated with the 3D structure of moPrP. Furthermore, the present study clearly demonstrated three pH-sensitive sites in moPrP, i.e., (1) the N-terminal tertiary contact site of H1, (2) the C-terminal end of H1, and (3) the S2 region. In particular, among these pH-sensitive sites, the N-terminal tertiary contact region of H1 was found to be the most pH-sensitive one and was easily converted to a flexible structure by a slight decrease of pH in the solution. These data provided molecular evidence to explain the cellular mechanism for conversion from PrP(C) to PrP(Sc) in acidic organelles such as the endosome. 相似文献
184.
185.
Purification and characterization of a hemolysin-like protein, Sll1951, a nontoxic member of the RTX protein family from the Cyanobacterium Synechocystis sp. strain PCC 6803 下载免费PDF全文
The hemolysin-like protein (HLP) Sll1951, characterized by the GGXGXDXUX nonapeptide motif implicated in Ca(2+) binding, was purified from the glucose-tolerant strain (GT) of Synechocystis sp. strain PCC 6803. HLP was eluted at 560 kDa after gel filtration chromatography. Atomic absorption spectroscopy indicated that the protein bound calcium. The bound Ca(2+) was not chelated with EGTA; however, it was released after being heated at 100 degrees C for 1 min, and it rebound to the Ca(2+)-depleted protein at room temperature. The apparent HLP molecular mass increased to 1,000 kDa and reverted to 560 kDa during the release and rebinding of Ca(2+), respectively. The monomers of the respective forms appeared at 90 and 200 kDa after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. HLP showed no apparent hemolytic activity against sheep erythrocytes; however, a slight hemolytic activity was detected during the conformational change caused by the rebinding of Ca(2+). Immunoelectron microscopy using polyclonal antibodies against the 200-kDa monomer revealed that HLP is located in the cell surface layer. The localization and Ca(2+)-induced reversible conformational change suggest that HLP is a member of the repeat in toxin (RTX) protein family despite its latent and low toxicity. In some other cyanobacteria, RTX proteins are reported to be necessary for cell motility. However, the GT was immotile. Moreover, the motile wild-type strain did not express any HLP, suggesting that HLP is one of the factors involved in the elimination of motility in the GT. We concluded that the involvement of RTX protein in cyanobacterial cell motility is not a general feature. 相似文献
186.
Jun Hosogi Hideyuki Tanaka Kazuhiro Fujita Takashi Kuwabara Shigeo Ikegawa Norihiro Kobayashi Nariyasu Mano Junichi Goto 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(2):222-227
Determination of estrogens in plasma is important in evaluation of effects of some anticancer drugs, such as aromatase inhibitors. However, as reported previously, high performance liquid chromatography–radio immunoassay (HPLC–RIA) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) with chemical derivatization require complicated sample preparation. In this study, a highly sensitive and simple method for determination of estrone (E1), 17β-estradiol (E2) and estrone 3-sulfate (E1S) in human plasma has been developed. Following diethylether extraction from plasma, analytes were purified by immunosorbents and then determined by LC–MS/MS using electrospray ionization (ESI). Immunosorbents were prepared by immobilization of specific antibodies raised against each analyte onto solid support. Use of selective immunosorbents in sample preparation removed interference in plasma samples that would cause ionization suppression, and markedly improved the sensitivity of LC–MS/MS for these analytes, without derivatization. Calibration curves of each analyte showed good linearity and reproducibility over the range of 0.05–50 pg/injection for E1, 0.2–50 pg/injection for E2 and 0.05–300 pg/injection for E1S, respectively. The mean values of lower limits of quantification (LLOQ) in human plasma corrected by recovery of deuterated estrogens (internal standard, I.S.) were 0.1892 pg/mL for E1, 0.7064 pg/mL for E2 and 0.3333 pg/mL for E1S, respectively. These LLOQ values were comparable to those previous reported using HPLC–RIA and LC–MS/MS. Using this method, the normal levels of three estrogens in healthy female plasma (n = 5) were determined. The mean values of E1, E2 and E1S were 38.0 pg/mL (range 24.8–53.0), 34.3 pg/mL (22.6–46.6) and 786 pg/mL (163–2080), respectively. The immunoaffinity LC–MS/MS described here allows sensitive and accurate quantification of E1, E2 and E1S without laborious sample preparation. 相似文献
187.
Aritomi K Kuwabara T Tanaka Y Nakano H Yasuda T Ishikawa F Kurosawa H Kakiuchi T 《Microbiology and immunology》2010,54(11):691-701
The roles of chemokines CCL19 and CCL21 in Ab production were investigated using plt mutant mice, which lack expression of CCL19 and CCL21-ser in their lymphoid organs. In these mice, the Th response has been shown to tend towards the Th1 type because of accumulation of inflammatory dendritic cells. When plt mice were immunized with 100 μg OVA in CFA, the number of Ab-forming cells in the draining LN, and serum concentrations of OVA-specific IgM and IgG Ab, were very close to those of the control, yet IgG2a Ab in plt mice was increased. In vitro IFN-γ production by the draining LN cells of plt mice was increased. In addition, the ability of helper T cells from plt mice to stimulate Ab production in vitro was prolonged. Also, in the plt mice, in vivo challenge with OVA in incomplete Freund's adjuvant elicited a stronger IgG2a response and a weaker IgG1 response, which is suggestive of a Th1-dominant response. Similar findings were obtained when mice were immunized with 100 μg OVA in alum, except that with alum the increases observed in plt mice were IgG1 produced in vivo and IL-4 produced in vitro by draining LN cells. Furthermore, immunization with alum adjuvant also induced a prolonged in vitro recall response of IFN-γ and IL-4. These findings indicate that plt mice mount an anti-OVA Ab response, and suggest that CCL19 and CCL21 induce prompt Ab responses to antigen, and negatively regulate helper T cell responses in vivo. 相似文献
188.
189.
Kristensen A. G. Shibuya K. Amino H. Misawa S. Sekiguchi Y. Suzuki Y. Suichi T. Tsuneyama A. Nakamura K. Kuwabara S. 《Neurophysiology》2020,52(2):134-139
Neurophysiology - Excitability properties at the motor point of the abductor digiti minimi (ADM) muscle were measured using an accelerometer placed on the little finger tip in 31 healthy subjects,... 相似文献
190.
Haruka Ohashi Masae Saito Reiko Horie Hiroshi Tsunoda Hiromu Noba Haruka Ishii Takashi Kuwabara Yutaka Hiroshige Shinsuke Koike Yoshinobu Hoshino Hiroto Toda Koichi Kaji 《European Journal of Wildlife Research》2013,59(2):167-177
Over the last century, human activity has caused significant changes to the activity patterns of many wildlife species. The wild boar is one species known to change its activity pattern with the intensity of human disturbance. We conducted camera trap surveys in two study sites, Shingo and Himuro, in Tochigi, central Japan. We investigated effects of two types of human disturbance on the activity pattern of a wild boar population: ‘direct’ disturbance related to hunting activity and ‘indirect’ disturbance related to daily human activity. In the hunting season, relative abundance indices (RAI) of wild boars significantly decreased, and the proportion of activity at night increased compared with the nonhunting season. RAI of wild boars at night decreased with increasing distance from the settlement, while RAI of wild boars during the day did not. Relative proportion of activity at night was higher in cameras at 0–200 m from the settlements, while no significant pattern was found in cameras far from settlements. Both direct and indirect effects of human activity had a significant effect on the activity pattern of wild boars. A decrease in human activity may result in the rapid expansion of wild boar populations, and re-evaluation of the human factor is important for more intelligent management of wild boar populations and to solve the human–wildlife conflict. 相似文献