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101.
Hideaki Fujii Satomi Imaide Shigeto Hirayama Toru Nemoto Hiroaki Gouda Shuichi Hirono Hiroshi Nagase 《Bioorganic & medicinal chemistry letters》2012,22(24):7711-7714
To clarify the essential structures of an opioid κ receptor selective agonist, nalfurafine, for binding to the κ receptor, we designed and synthesized the decahydro(iminoethano)phenanthrene derivatives with an oxygen functionality at the 3-position. The introduction of a hydroxy group to the derivatives increased the affinity and selectivity to the κ receptor regardless of the configuration at the 3-position. However, their affinities were lower than those of nalfurafine with the phenolic hydroxy group. The results suggested that the acidity of the hydroxy group would play an important role in the interaction with the opioid receptor. The low affinities of the 3-keto derivatives indicated that the 3-hydroxy group may participate in the hydrogen bonding with the receptor site not as a hydrogen acceptor but as a hydrogen donor. This is the first experimental evidence for a role as a hydrogen donor for the 3-hydroxy group in morphinans. Furthermore, the κ selectivities in these derivatives with the 6α-amide side chain were affected by the the 3-hydroxy group. The obtained structure–activity relationship information is expected to be useful for the design of more selective ligands for the κ receptor. 相似文献
102.
Iwai S Kikuchi T Kasahara N Teratani T Yokoo T Sakonju I Okano S Kobayashi E 《PloS one》2012,7(3):e33157
Background
The aim of this study was to investigate factors that may improve the condition of a marginal kidney preserved with a normothermic solution following cardiac death (CD) in a model of rat kidney transplantation (RTx).Methods
Post-euthanasia, Lewis (LEW) donor rats were left for 1 h in a 23°C room. These critical kidney grafts were preserved in University of Wisconsin (UW), lactate Ringer''s (LR), or extracellular-trehalose-Kyoto (ETK) solution, followed by intracellular-trehalose-Kyoto (ITK) solution at 4, 23, or 37°C for another 1 h, and finally transplanted into bilaterally nephrectomized LEW recipient rats (n = 4–6). Grafts of rats surviving to day 14 after RTx were evaluated by histopathological examination. The energy activity of these marginal rat kidneys was measured by high-performance liquid chromatography (HPLC; n = 4 per group) and fluorescence intensity assay (n = 6 per group) after preservation with UW or ETK solutions at each temperature. Finally, the transplanted kidney was assessed by an in vivo luciferase imaging system (n = 2).Results
Using the 1-h normothermic preservation of post-CD kidneys, five out of six recipients in the ETK group survived until 14 days, in contrast to zero out of six in the UW group (p<0.01). Preservation with ITK rather than ETK at 23°C tended to have an inferior effect on recipient survival (p = 0.12). Energy activities of the fresh donor kidneys decreased in a temperature-dependent manner, while those of post-CD kidneys remained at the lower level. ETK was superior to UW in protecting against edema of the post-CD kidneys at the higher temperature. Luminescence intensity of successful grafts recovered within 1 h, while the intensity of grafts of deceased recipients did not change at 1 h post-reperfusion.Conclusions
Normothermic storage with extracellular-type solution containing trehalose might prevent reperfusion injury due to temperature-dependent tissue edema. 相似文献103.
104.
Erika Kubo Ayuko Sato Noriko Yoshikawa Satomi Kagota Kazumasa Shinozuka Kazuki Nakamura 《Central European Journal of Biology》2012,7(1):167-171
Cordyceps sinensis is a Chinese medicinal fungus traditionally used in cancer treatments. In a previous study, we investigated the antimetastatic
activity of Cordyceps sinensis (WECS) extract using liver metastatic model mice injected with B16-F0 mouse melanoma cells into the spleen. WECS reduced
the number of metastatic nodules of B16-F0 cells in the liver of C57BL/6 mice, and significantly prolonged survival of the
mice. Furthermore, we examined the effects of WECS on hepatocyte growth factor (HGF)-accelerated invasion of B16-F0 cells
using a chemo-invasion assay in vitro. WECS was shown to significantly reduce HGF-accelerated B16-F0 cell invasion. In the present study, we investigated the effect
of WECS on Tissue Inhibitor of Metalloproteinase (TIMP)-1 secretion from B16-F0 cells in order to identify clues to the mechanism
underlying the anti-invasive action of WECS. As a result, WECS significantly increased the secretion of TIMP-1 from B16-F0
cells. Moreover, we investigated the effect of cordycepin (3′-deoxyadenosine), a component of WECS, on TIMP-1 secretion from
B16-F0 cells to potentially identify the pharmacologically active ingredient in WECS extract. Cordycepin was shown to significantly
accelerate the release of TIMP-1 from cells. These findings suggest that WECS exerts anti-invasive activity, in part by increasing
TIMP-1 secretion from melanoma cells, and that cordycepin potentially functions as the effective component. 相似文献
105.
Ito M Nakajima S Fujisawa D Miyashita M Kim Y Shear MK Ghesquiere A Wall MM 《PloS one》2012,7(2):e31209
Background
Complicated grief, which is often under-recognized and under-treated, can lead to substantial impairment in functioning. The Brief Grief Questionnaire (BGQ) is a 5-item self-report or interview instrument for screening complicated grief. Although investigations with help-seeking samples suggest that the BGQ is valid and reliable, it has not been validated in a broader population.Methodology/Principal Findings
A questionnaire was mailed to a randomly selected sample (n = 5000) residing in one of 4 areas of Japan. The BCQ was examined for responders who were bereaved more than 6 months and less than 10 years (n = 915). Non-specific psychological distress was assessed with the K6 screening scale. Multiple group confirmatory factor analysis supported a uni-dimensional factor structure and the invariance of parameters across gender and age. Cronbach''s alpha was sufficiently high (alpha = .75) to confirm internal consistency. Average Variance Extracted (0.39) was higher than the shared covariance (0.14) between BGQ and K6, suggesting discriminant validity.Conclusions
The results of this study support the reliability and validity of the BGQ in the Japanese population. Future studies should examine predictive validity by using structured interviews or more detailed scales for complicated grief. 相似文献106.
Ohi K Hashimoto R Yasuda Y Nemoto K Ohnishi T Fukumoto M Yamamori H Umeda-Yano S Okada T Iwase M Kazui H Takeda M 《PloS one》2012,7(1):e29780
Background
The rs12807809 single-nucleotide polymorphism in NRGN is a genetic risk variant with genome-wide significance for schizophrenia. The frequency of the T allele of rs12807809 is higher in individuals with schizophrenia than in those without the disorder. Reduced immunoreactivity of NRGN, which is expressed exclusively in the brain, has been observed in Brodmann areas (BA) 9 and 32 of the prefrontal cortex in postmortem brains from patients with schizophrenia compared with those in controls.Methods
Genotype effects of rs12807809 were investigated on gray matter (GM) and white matter (WM) volumes using magnetic resonance imaging (MRI) with a voxel-based morphometry (VBM) technique in a sample of 99 Japanese patients with schizophrenia and 263 healthy controls.Results
Although significant genotype-diagnosis interaction either on GM or WM volume was not observed, there was a trend of genotype-diagnosis interaction on GM volume in the left anterior cingulate cortex (ACC). Thus, the effects of NRGN genotype on GM volume of patients with schizophrenia and healthy controls were separately investigated. In patients with schizophrenia, carriers of the risk T allele had a smaller GM volume in the left ACC (BA32) than did carriers of the non-risk C allele. Significant genotype effect on other regions of the GM or WM was not observed for either the patients or controls.Conclusions
Our findings suggest that the genome-wide associated genetic risk variant in the NRGN gene may be related to a small GM volume in the ACC in the left hemisphere in patients with schizophrenia. 相似文献107.
Ohi K Hashimoto R Nakazawa T Okada T Yasuda Y Yamamori H Fukumoto M Umeda-Yano S Iwase M Kazui H Yamamoto T Kano M Takeda M 《PloS one》2012,7(4):e35696
Background
Hypofunction of the glutamate N-Methyl-d-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. p250GAP is a brain-enriched NMDA receptor-interacting RhoGAP. p250GAP is involved in spine morphology, and spine morphology has been shown to be altered in the post-mortem brains of patients with schizophrenia. Schizotypal personality disorder has a strong familial relationship with schizophrenia. Several susceptibility genes for schizophrenia have been related to schizotypal traits.Methods
We first investigated the association of eight linkage disequilibrium-tagging single-nucleotide polymorphisms (SNPs) that cover the p250GAP gene with schizophrenia in a Japanese sample of 431 schizophrenia patients and 572 controls. We then investigated the impact of the risk genetic variant in the p250GAP gene on schizotypal personality traits in 180 healthy subjects using the Schizotypal Personality Questionnaire.Results
We found a significant difference in genotype frequency between the patients and the controls in rs2298599 (χ2 = 17.6, p = 0.00015). The minor A/A genotype frequency of rs2298599 was higher in the patients (18%) than in the controls (9%) (χ2 = 15.5, p = 0.000083). Moreover, we found that subjects with the rs2298599 risk A/A genotype, compared with G allele carriers, had higher scores of schizotypal traits (F1,178 = 4.08, p = 0.045), particularly the interpersonal factor (F1,178 = 5.85, p = 0.017).Discussion
These results suggest that a genetic variation in the p250GAP gene might increase susceptibility not only for schizophrenia but also for schizotypal personality traits. We concluded that the p250GAP gene might be a new candidate gene for susceptibility to schizophrenia. 相似文献108.
Tanaka K Yokoi S Morimoto K Iwata T Nakamoto Y Nakayama K Koyama K Fujiwara T Fukase K 《Bioorganic & medicinal chemistry》2012,20(6):1865-1868
Versatile method for living cell labeling has been established. Cell surfaces are initially biotinylated by azaelectrocyclization, and then treated with the fluorescence-labeled avidin or the anti-biotin antibody. 相似文献
109.
Xia Han Hideyuki Tomitori Satomi Mizuno Kyohei Higashi Christine Füll Tomohide Fukiwake Yusuke Terui Pathama Leewanich Kazuhiro Nishimura Toshihiko Toida Keith Williams Keiko Kashiwagi Kazuei Igarashi 《Journal of neurochemistry》2008,107(6):1566-1577
The binding of spermine and ifenprodil to the amino terminal regulatory (R) domain of the N‐methyl‐D ‐aspartate receptor was studied using purified regulatory domains of the NR1, NR2A and NR2B subunits, termed NR1‐R, NR2A‐R and NR2B‐R. The R domains were over‐expressed in Escherichia coli and purified to near homogeneity. The Kd values for binding of [14C]spermine to NR1‐R, NR2A‐R and NR2B‐R were 19, 140, and 33 μM, respectively. [3H]Ifenprodil bound to NR1‐R (Kd, 0.18 μM) and NR2B‐R (Kd, 0.21 μM), but not to NR2A‐R at the concentrations tested (0.1–0.8 μM). These Kd values were confirmed by circular dichroism measurements. The Kd values reflected their effective concentrations at intact NR1/NR2A and NR1/NR2B receptors. The results suggest that effects of spermine and ifenprodil on NMDA receptors occur through binding to the regulatory domains of the NR1, NR2A and NR2B subunits. The binding capacity of spermine or ifenprodil to a mixture of NR1‐R and NR2A‐R or NR1‐R and NR2B‐R was additive with that of each individual R domain. Binding of spermine to NR1‐R and NR2B‐R was not inhibited by ifenprodil and vice versa, indicating that the binding sites for spermine and ifenprodil on NR1‐R and NR2B‐R are distinct. 相似文献
110.
Kanatsu-Shinohara M Takehashi M Takashima S Lee J Morimoto H Chuma S Raducanu A Nakatsuji N Fässler R Shinohara T 《Cell Stem Cell》2008,3(5):533-542
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis. In a manner comparable to hematopoietic stem cell transplantation, SSCs colonize the niche of recipient testes and reinitiate spermatogenesis following microinjection into the seminiferous tubules. However, little is known about the homing mechanism of SSCs. Here we examined the role of adhesion molecules in SSC homing. SSCs isolated from mice carrying loxP-tagged beta1-integrin alleles were ablated for beta1-integrin expression by in vitro adenoviral cre transduction. The beta1-integrin mutant SSCs showed significantly reduced ability to recolonize recipient testes in vivo and to attach to laminin molecules in vitro. In contrast, genetic ablation of E-cadherin did not impair homing, and E-cadherin mutant SSCs completed normal spermatogenesis. In addition, the deletion of beta1-integrin on Sertoli cells reduced SSC homing. These results identify beta1-integrin as an essential adhesion receptor for SSC homing and its association with laminin is critical in multiple steps of SSC homing. 相似文献