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61.
62.
Hoshino Y Koide H Furuya K Haberaecker WW Lee SH Kodama T Kanazawa H Oku N Shea KJ 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(1):33-38
Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes. 相似文献
63.
Umetsu H Kaneko N Yoshihara A Sakuma S Hanada N Miyazaki H 《Oral health & preventive dentistry》2012,10(2):161-166
Purpose: To determine whether variation in glucan synthesis by Streptococcus mutans isolates is associated with caries development in children receiving a fluoride mouth rinse (FMR). Materials and Methods: Of 122 children (aged 9 to 10 years), 64 had received FMR (FMR(+) group) and the remaining 58 children had not (FMR(-) group). The number of decayed and filled teeth (DFT) and increases in the number of DFT in 1 year (dDFT) were recorded. Saliva samples were collected to isolate the clinical S. mutans strains. The isolates were incubated in heart infusion broth supplemented with 1% sucrose, then the amount of water-insoluble glucan (WIG) formed on a glass tube surface was evaluated. Results: In the FMR(-) group, children carrying S. mutans had a higher DFT (P = 0.039) and tended to have a higher dDFT (P = 0.080) than the others. In the FMR(+) group, although the differences between children with and without S. mutans were not significant, children carrying S. mutans that produced a high amount of WIG had higher dDFT than the other S. mutans-positive children (P = 0.034). Conclusions: This study revealed that the variation in glucan synthesis by S. mutans is associated with caries development in children receiving a FMR. 相似文献
64.
Swallowing disorders are a common complaint among the elderly. Recently, surface electrical stimulation applied to the neck
region has received increased attention as a new modality to treat pharyngeal dysphagia. Previous reports used pulsed current
at a frequency range of 1-120 Hz. Kilohertz-frequency alternating currents (ACs) have not been tested for treating dysphagia.
Therefore, we evaluated the effects of interferential currents (IFCs), the most popular modality of amplitude-modulated kilohertz-frequency
ACs in clinical practice, on the swallowing reflex in healthy subjects. We found that IFC stimulation at the sensory threshold
with 50-Hz modulation significantly increased the number of swallows without any discomfort, but pure AC stimulation at the
carrier frequency did not have a significant effect. There was no statistically significant difference in the time course
of the number of swallows among 1,000-, 2,000-, 4,000-, and 6,000-Hz carrier frequencies. The number of swallows remained
increased during the 15-min IFC stimulation, suggesting that IFC stimulation facilitates the swallowing reflex without adaptation,
at least during this stimulation period. We suggest that an IFC stimulation or a low-frequency, modulated kilohertz AC stimulation,
which would be more comfortable than pulsed currents, is an alternative stimulation mode for treating pharyngeal dysphagia. 相似文献
65.
66.
Itonaga H Tsushima H Hata T Matsuo E Imanishi D Imaizumi Y Kawaguchi Y Fukushima T Doi Y Mori S Kamihira S Tomonaga M Miyazaki Y 《International journal of hematology》2012,95(2):209-213
The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation. 相似文献
67.
Oku Kazuma Tokutsu Kei Matsuda Shinya Kondo Hiroyuki 《Japanese journal of ophthalmology》2021,65(6):797-802
Japanese Journal of Ophthalmology - To determine the incidence of rhegmatogenous retinal detachments (RRDs) and proliferative vitreoretinopathies (PVRs) and their distribution by age and sex in... 相似文献
68.
Kenji Matsuda Tsukasa Hotta Katsunari Takifuji Shozo Yokoyama Yoshimasa Oku Tadamichi Hashimoto Hiromitsu Iwamoto Hiroki Yamaue 《Surgery today》2013,43(9):984-989
Purposes
The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC.Methods
Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively.Results
A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p < 0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001).Conclusion
Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy. 相似文献69.
Jun Takahashi Hirokazu Kobayashi Shinji Wakabayashi Masao Deguchi Hidehiro Ito Yuji Mogami Hirotaka Tanikawa Hiroyuki Nakagawa Hideki Moriya Ryohei Ashizawa Kenji Takahara Hisatoshi Kinoshita Yutaka Tateiwa Hiromichi Misawa Takahiro Tsutsumimoto Taku Nakakohji Yohei Yuzawa Akihito Sawaumi Yohei Hidai Satoshi Matsuda Isao Nakamura Shigeyuki Toba Mikio Kamimura Takeshi Nakane Hiroki Hirabayashi Hiroyuki Hashidate Nobuhide Ogihara Keijiro Mukaiyama Hiroyuki Kato Kuniyoshi Ohtsuka 《Journal of orthopaedic science》2013,18(2):208-215
Background
Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D).Methods
QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after ≥6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0–100).Results
Leg pain, leg numbness, and low back pain while walking (VAS ≥25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time <15 min. The mean EQ-5D utility value for QOL was 0.59 ± 0.12. This value was significantly associated with maximum walking time (p = 0.030) based on classification of patients into groups with walking times <7.5, 7.5–15, 15–30, and >30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by ≥10 min and the EQ-5D utility value was improved by ≥0.1 points in significantly more patients in the limaprost group than in the control group.Conclusion
According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects. 相似文献70.