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Tsuyoshi Ozawa MD Shinsuke Kazama MD PhD Takashi Akiyoshi MD PhD Koji Murono MD Satomi Yoneyama MD PhD Toshiaki Tanaka MD PhD Junichiro Tanaka MD PhD Tomomichi Kiyomatsu MD PhD Kazushige Kawai MD PhD Hiroaki Nozawa MD PhD Takamitsu Kanazawa MD PhD Hironori Yamaguchi MD PhD Soichiro Ishihara MD PhD Eiji Sunami MD PhD Joji Kitayama MD PhD Teppei Morikawa MD PhD Masashi Fukayama MD PhD Toshiaki Watanabe MD PhD 《Annals of surgical oncology》2014,21(8):2650-2658
Background
The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.Methods
The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.Results
Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).Conclusions
Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC. 相似文献85.
Ana C. Issy João Francisco C. Pedrazzi Bruno H. Yoneyama Elaine A. Del-Bel 《Psychopharmacology》2014,231(4):663-672
Rationale
Nitric oxide (NO) modulates the dopamine uptake and release processes and appears to be implicated in dopamine-related pathologies, such as schizophrenia. However, it is unclear whether there is excess or deficient NO synthesis in schizophrenia pathophysiology. Analyses of the intracellular pathways downstream of NO system activation have identified the cyclic nucleotide cyclic guanosine monophosphate (cGMP) as a possible target for drug development. Defects in the sensorimotor gating of the neural mechanism underlying the integration and processing of sensory information have been detected across species through prepulse inhibition (PPI).Objectives
The aim of this study was to investigate the effects of NO/cGMP increase on sensorimotor gating modulation during dopamine hyperfunction.Methods
Mice were treated with NO donors and subjected to the PPI test. Treatment with the NO donor sodium nitroprusside was preceded by pretreatment with a soluble guanylate cyclase (sGC) inhibitor. Additionally, the mice were treated with NO donors and phosphodiesterases inhibitors prior to amphetamine treatment.Results
Pretreatment with the NO donors enhanced the PPI response and attenuated the amphetamine-disruptive effects on the PPI. The sGC inhibitor did not modify the sodium nitroprusside effects. Additionally, the cGMP increase induced by a specific phosphodiesterase inhibitor did not modify the amphetamine-disruptive effect.Conclusions
This study provides the first demonstration that an increase in NO can improve the PPI response and block the amphetamine-disruptive effects on the PPI response. Our data are consistent with recent clinical results. However, these effects do not appear to be related to an increase in cGMP levels, and further investigation is thus required. 相似文献86.
Takashi Mitsuki Muneyoshi Kimura Hideki Araoka Kosei Kageyama Shinsuke Takagi Go Yamamoto Shigeki Nakamura Yoshitsugu Miyazaki Naoyuki Uchida Akiko Yoneyama Shuichi Taniguchi 《Journal of infection and chemotherapy》2019,25(4):289-292
Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT. 相似文献
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BACKGROUND AND AIMS: GH has profound effects on body composition and lipid metabolism in children as well as in adults. The relationship between such metabolic effects and the growth-promoting effects of GH has not been studied thoroughly in children with GH deficiency. This prospective study was designed to determine the relationship between growth and lipid metabolism during long-term GH treatment. PATIENTS AND METHODS: Twenty-two boys with idiopathic GH deficiency were studied. Height, per cent overweight (%OW), per cent body fat (%BF) and serum low-density lipoprotein (LDL) cholesterol levels were determined every 6 months during 3 years of GH treatment. RESULTS: After 3 years of GH treatment, the mean height SD score had increased significantly from -2.70 SD to -1.59 SD (P < 0.0001), while the mean %OW and LDL cholesterol level had decreased significantly from 7.0% to 1.3% (P < 0.0001) and from 2.69 mmol/l to 2.04 mmol/l (P < 0.0001), respectively. The mean %BF fell significantly from 15.5% to 11.1% during the first 6 months of GH treatment (P < 0.0001). The 6-month reduction in %BF correlated significantly with the 3-year increase in height SD score (r = -0.58, P = 0.008). The decrease in %OW also correlated negatively with the change in height SD score (r = -0.48, P = 0.03). However, there was no correlation between the changes in LDL cholesterol levels and those in %BF, %OW or height SD score. CONCLUSION: We conclude that the growth-promoting effects of GH correlate significantly with the reductions in %BF and %OW but not with the decrease in LDL cholesterol level in children with GH deficiency. The changes in LDL cholesterol did not correlate with any of the changes in body composition parameters, suggesting that the various actions of GH may have different mechanisms of regulation. 相似文献
88.
Background: Falls cause serious problems for the elderly. Sleep problems impair the control of postural balance and cause falls, and lack of sleep induces sleepiness, which in turn causes inattentiveness. The present study aims to clarify the relation between sleep disorders and falls among the community-dwelling elderly and to determine whether or not sleep disorder is an independent risk factor for falls.
Methods: Of 2274 community-dwelling persons aged 65 and older who participated in the first study in July 1998, 1771 (77.9%) who responded to the questions concerning sleep disorders were the subjects in the present study.
Results: There were 1521 persons (85.9%) who had not experienced any fall during the past year, 194 (11.0%) who had one or two falls, 27 (1.5%) had three to four falls and 29 (1.6%) had more than five falls. The relation between the history of falls and the sleep problems indicates that the odds ratio for the history of falls was significantly higher if the nocturnal sleep disorder was more intense ( P < 0.001) and the sleep hours during the day were longer ( P < 0.01). In order to determine the independent risk factors for falls, the general linear model analysis was conducted using the significantly different background. The nocturnal sleep problems ( F = 4.05; P = 0.018), the daytime sleep ( F = 4.17; P = 0.016) and nocturnal sleep problems and interaction between (*) daytime sleep ( F = 2.54; P = 0.038) were significant independent explanatory variables as the age ( F = 14.4; P < 0.001), difficulty in walking ( F = 4.30; P = 0.038), history of stroke ( F = 64.1; P < 0.001) and arthralgia ( F = 5.31; P = 0.021).
Conclusion: The data emphasize that the sleep disorder is closely related to falls. 相似文献
Methods:
Methods: Of 2274 community-dwelling persons aged 65 and older who participated in the first study in July 1998, 1771 (77.9%) who responded to the questions concerning sleep disorders were the subjects in the present study.
Results:
Results: There were 1521 persons (85.9%) who had not experienced any fall during the past year, 194 (11.0%) who had one or two falls, 27 (1.5%) had three to four falls and 29 (1.6%) had more than five falls. The relation between the history of falls and the sleep problems indicates that the odds ratio for the history of falls was significantly higher if the nocturnal sleep disorder was more intense ( P < 0.001) and the sleep hours during the day were longer ( P < 0.01). In order to determine the independent risk factors for falls, the general linear model analysis was conducted using the significantly different background. The nocturnal sleep problems ( F = 4.05; P = 0.018), the daytime sleep ( F = 4.17; P = 0.016) and nocturnal sleep problems and interaction between (*) daytime sleep ( F = 2.54; P = 0.038) were significant independent explanatory variables as the age ( F = 14.4; P < 0.001), difficulty in walking ( F = 4.30; P = 0.038), history of stroke ( F = 64.1; P < 0.001) and arthralgia ( F = 5.31; P = 0.021).
Conclusion:
Conclusion: The data emphasize that the sleep disorder is closely related to falls. 相似文献
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90.
Kamimura Kiyohisa Nakajo Masanori Yoneyama Tomohide Fukukura Yoshihiko Fujio Shingo Goto Yuko Iwanaga Takashi Akamine Yuta Yoshiura Takashi 《European radiology》2020,30(4):1908-1917
European Radiology - To evaluate the feasibility of assessment of microvessel perfusion of pituitary adenomas with intravoxel incoherent motion (IVIM) imaging using single-shot turbo... 相似文献