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Effectiveness of Cross‐Linked Gelatin Glue in Canine Lung Surgery Models.
Get PDFBackground. Air leakage is a common postoperative complication in pulmonary surgery, and surgical sealants have been developed to prevent or reduce the incidence of air leaks. In this study, we evaluated the efficacy of cross-linked gelatin glue (gelatin plus glutaraldehyde) in canine lung surgery models. Methods. Pulmonary fistulas and injuries were created in dogs and sealed with gelatin glue, fibrin glue, or fibrin glue with a polyglycolic acid (PGA) sheet. Seal-breaking pressures were measured in the fistula model, and pleural adhesions were assessed 28 days postoperatively in the lung injury model. Results. The seal-breaking pressures for canine cadaver and living lung surgeries (; the maximum pressures were 80 and 40 cm H₂O) were respectively: gelatin glue, 77 ± 6 and 32.3 ± 8.9cm H₂O; fibrin glue using spray, 39.2 ± 9.3 and 32 ± 6cm H₂O; fibrin glue using the rub-and-soak method, 35 ± 13.4 and 40 ± 0 cm H₂O; and fibrin glue with a PGA sheet, 55.5 ± 18.2 and 39 ± 2cm H₂O. In the lung injury model, there were no chest wall adhesions in the gelatin and fibrin glue alone groups, while strong adhesions were observed when treated with fibrin glue with a PGA sheet. Conclusions. Gelatin glue's sealing effect was superior to that of fibrin glue while preventing postoperative pleural adhesions. These findings suggest that gelatin glue may be effective as a surgical sealant or anti-adhesion materialin lung surgery
超吸水性ポリマー球状塞栓物質の高張食塩水を用いた膨潤抑制法の開発
Get PDFPURPOSE: To analyze size changes of superabsorbent polymer (SAP) microspheres with the reduced expansion technique, and to evaluate pharmacological advantages of transarterial chemoembolization using cisplatin-loaded SAP microspheres with the reduced expansion technique. MATERIALS AND METHODS: In an in vitro study, diluted contrast materials containing different concentrations of sodium ions were examined to expand SAP microspheres and determined the reduced expansion technique. Size distributions of cisplatin-loaded SAP microspheres were analyzed. In an in vivo study, TACE was performed using cisplatin-loaded SAP microspheres with the reduced expansion and control techniques in 18 VX2 rabbits. RESULTS: The degree of expansion was reduced to the greatest extent by using a mixture of non-ionic contrast material and 10% NaCl at a 4:1 ratio. The mean diameter of the reduced expansion of cisplatin-loaded SAP microspheres was 188.4 μm, while that of the control expansion was 404.9 μm. The plasma platinum concentrations of the reduced expansion group at 5 min after TACE were significantly higher than those of the control expansion group (2.19 ± 0.77 vs. 0.75 ± 0.08 μg/mL, P = .01). The tumor platinum concentrations of the reduced expansion group at 1 h were significantly higher than those of the control expansion group (10.76 ± 2.57 vs. 1.57 ± 0.14 μg/g, P = .044). CONCLUSION: The expanding level of SAP microspheres can be reduced by using hypertonic saline. Cisplatin-loaded SAP microspheres with the reduced expansion technique have the advantages of achieving higher cisplatin tissue concentration in TACE for liver tumors.博士（医学）・甲第709号・令和元年6月26日© Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2018This is a post-peer-review, pre-copyedit version of an article published in Cardiovascular and interventional radiology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00270-018-1990-4
胃癌におけるクローディン4標的化によるシスプラチン化学療法感受性の向上
Get PDFClaudins are major tight-junction proteins that mediate cellular polarity and differentiation. The present study investigated whether the 4D3 antibody to the human CLDN4 extracellular domain (that we previously established) is capable of modulating chemotherapeutic sensitivity in gastric cancer (GC). The results of the present study showed that CLDN4 was overexpressed in 137 of the 192 analyzed GC cases, and that CLDN4 expression was retained in tumors of a lower histological grade (more differentiated), and/or those that were caudal-type homeobox protein 2 (CDX2)-positive, but was reduced in more highly undifferentiated, and CDX2-negative GC cases. The study also compared the synergic effects of combining 4D3 with CDDP treatment and knocking down CLDN4 expression in MKN74 and TMK-1 human GC cells. Co-treatment with 4D3 increased anti-tumor effects of CDDP, whereas CLDN4 knockdown did not. In the TMK-1 cells, non-tight junction CLDN4 associated with integrin β1, increasing stem cell-associated proteins via FAK-c-SRC signals. The anti-tumoral effect of CDDP and 4D3 was examined in a nude mouse subcutaneous tumor model. In the two GC cell lines, concurrent treatment with 4D3 and CDDP synergistically inhibited cell proliferation and increased tumor necrosis and apoptosis to a greater degree than CDDP treatment alone. These findings suggest that 4D3 might increase chemotherapeutic sensitivity by evoking structural disintegration of tight-junction CLDN4 expressed in gastric cancer.博士（医学）・甲第713号・令和元年6月26日Copyright: Nishiguchi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC
BY 3.0 https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
スルフォラファンの肝癌発育抑制効果および血管新生抑制効果に関する基礎的検討
Get PDFSulforaphane (SFN) exhibits inhibitory effects in different types of cancers. However, its inhibitory effect on liver cancer remains unknown. This study aimed to determine the therapeutic potential of SFN for the treatment of liver cancer and explore the functional mechanisms underlying the inhibitory effects of SFN. Water-Soluble Tetrazolium salt (WST-1) assay was performed to assess the in vitro effect of SFN on cell proliferation in the human liver cancer cell lines, HepG2 and Huh-7. The mRNA levels of Nrf2 target genes and cell cycle-related genes were determined using quantitative RT-PCR. For assessing the inhibitory effect of SFN in vivo, we injected immortalized liver cancer cells into BALB/c nude mice as a xenograft model. SFN was orally administrated daily after tumor inoculation and continued for thirty-five days until their sacrifices. Nrf2 activation, induced by SFN, was confirmed by mRNA upregulation of HO-1, MRP2, and NQO1 in both the cell lines. Significant inhibition of liver cancer cell proliferation by SFN was shown in vitro in a dose-dependent manner by the downregulation of CCND1, CCNB1, CDK1 and CDK2. In in vivo studies, the administration of SFN significantly reduced the subcutaneous tumor burdens at the end of experiments by suppressing tumor cell proliferation, confirmed by Ki67 immunohistochemical analysis. The mRNA levels of CCND1, CCNB1, CDK1 and CDK2 were also decreased in these SFNtreated xenograft tumors. Moreover, CD34 immunostaining elucidated that the intratumoral neovascularization was markedly attenuated in the SFN-treated xenograft tumors. SFN exerts inhibitory effect on human liver cancer cells with antiangiogenic activity. The earlier version of this study was presented at the meeting of AASLD Liver Learning on Oct 2017.博士（医学）・甲第707号・平成31年3月15日© The Author(s) 2018 Under License of Creative Commons Attribution 3.0 License https://creativecommons.org/licenses/by/3.0
がん登録データを用いた、小児がんの罹患率・死亡率の日英比較（1993-2010年）
Get PDFThe present study aimed to compare cancer incidence and trends in survival for children diagnosed in Japan and England, using population-based cancer registry data. The analysis was based on 5192 children with cancer (age 0-14 years) from 6 prefectural cancer registries in Japan and 21 295 children diagnosed in England during 1993-2010. Differences in incidence rates between the 2 countries were measured with Poisson regression models. Overall survival was estimated using the Kaplan-Meier method. Incidence rates for Hodgkin lymphoma, renal tumors and Ewing sarcomas in England were more than twice as high as those in Japan. Incidence of germ cell tumors, hepatic tumors, neuroblastoma and acute myeloid leukemia (AML) was higher in Japan than in England. Incidence of all cancers combined decreased in Japan throughout the period 1993 to 2010, which was mainly explained by a decrease in registration of neuroblastoma in infants. For many cancers, 5-year survival improved in both countries. The improvement in survival in chronic myeloid leukemia (CML) was particularly dramatic in both countries. However, 5-year survival remained less than 80% in 2005-2008 in both countries for AML, brain tumors, soft tissue sarcomas, malignant bone tumors and neuroblastoma (age 1-14 years). There were significant differences in incidence of several cancers between countries, suggesting variation in genetic susceptibility and possibly environmental factors. The decrease in incidence for all cancers combined in Japan was related to the cessation of the national screening program for neuroblastoma. The large improvement in survival in CML coincided with the introduction of effective therapy (imatinib).博士（医学）・乙第1425号・平成31年3月15日© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited
Multiplex PCRを用いた簡便で感度の高い溺死診断法の開発
Get PDFFor diagnosing death due to drowning, the method of acid digestion of diatoms is widely used to detect plankton in the organs of the corpse. However, the method is limited by its being complex, hazardous, time-consuming, and insufficiently sensitive. We therefore, developed a novel simple method to diagnose death due to drowning, and determined the location of drowning by detecting genes of representative bacteria in the environment. To procure all the information in one step, the multiplex PCR method was designed. For the diagnosis of drowning, the genes of upper respiratory indigenous bacteria, Streptococcus salivarius and Streptococcus sanguinis were used as indicators. For detection of the location of drowning, Aeromonas hydrophila and Microcystis aeruginosa were used as indicators of freshwater, and Vibrio harveyi as an indicator of seawater. A set of primers was designed for multiplex PCR. to amplify all the bacterial genes simultaneously. Using this method, 47 cases of drowning were examined, and the causes and locations of death were diagnosed.博士（医学）・乙第1428号・平成31年3月15
A Study on Visiting Restrictions in Intensive Care Units : Future Prospects for the Ideal Way of Japan from Foreign Literature.
Get PDF【目的】集中治療室(ICU)における面会制限に関して、国外の文献から研究の動向と実態を明らかにし、日本におけるICUの面会のあり方への示唆を得る。【方法】PubMed、CINAHLのデータベースを用いて、18論文を対象とした。【結果】ICUおよび病院施設を対象とした調査、面会制限の変更前後を比較検討した研究、ICU医療者と患者、家族を対象とした研究に分類された。国外では、面会制限を時問、回数だけでなく、待合室、情報提供などを含め報告していた。面会は、患者と家族の満足感の向上をもたらし、医療効果が得られたとの報告がある一方、看護師の負担や患者への有害要因との指摘もあった。【結論】日本におけるICUの面会制限について、家族の満足度、患者への医療効果、待合室等のアメニティー、情報提供体制などのシステムも含めて捉えることが今後の課題である。【Purpose】This study aimed to clarify trends in and status of research on visitation limitation in intensive care units (ICUs) by examining literature from abroad, and to obtain suggestions on ICU visitation policy in Japan.【Method】We examined 18 papers by using the PubMed and CINAHL databases. 【Results】Studies examined hospitals and ICUs; compared changes before and after implementing changes in visitation restrictions; and examined their impact on ICU staff, patients, and families. Further, studies conducted outside Japan have examined ICU visiting restrictions on the duration and frequency of visits, and they have assessed the provision of amenities such as waiting rooms and information provision systems. ICU visits were found to improve patients' and their family members' satisfaction levels, and medical effects were reported. However, some studies reported that visits were a burden on nurses and that they led to harmful effects on patients. 【Conclusion】Future challenges concerning visiting restrictions in ICUs in Japan pertain to the creation of systems to address family members' satisfaction, medical effects on patients, and provision of amenities such as waiting rooms and information provision systems
自閉スペクトラム小児由来リンパ芽球様細胞株を用いたグレリンの抗炎症作用の検討
Get PDFThe gut hormone ghrelin has been implicated in a variety of functional roles in the central nervous system through the brain-gut axis, one of which is an anti-inflammatory effect. An aberrant brain-gut axis producing immune dysfunction has been implicated in the pathobiology of autism spectrum disorder (ASD), and elevated expression of inflammatory markers has been shown in blood and brain tissue from subjects with ASD. We hypothesized that ghrelin may mitigate this effect. Lymphoblastoid cell lines from typically developed children (TD-C) (N = 20) and children with ASD (ASD-C) (N = 20) were cultured with PBS or human ghrelin (0.01 μM) for 24 h, and mRNA expression levels of the inflammation-related molecules interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B (NF-κB) were measured to examine the effects of ghrelin as an anti-inflammatory agent. Expression levels of TNF-α and NF-κB mRNA, but not IL-1β or IL-6, were significantly elevated in ASD-C compared to TD-C. Ghrelin showed a tendency to reduce the expression of TNF-α and NF-κB, but this was not statistically significant. Considering the heterogenous pathobiology of ASD, we examined the effects of ghrelin on TD-C and ASD-C with expression levels of TNF-α and NF-κB in the highest and lowest quartiles. We found that ghrelin markedly reduced mRNA expression of TNF-α and NF-κB s in ASD-C with highest-quartile expression, but there were no effects in ASD-C with lowest-quartile expression, TD-C with highest quartile expression, or TD-C with lowest quartile expression. Together, these findings suggest that ghrelin has potential as a novel therapeutic agent for ASD with inflammation and/or immune dysfunction.博士（医学）・甲第719号・令和元年9月27日Copyright © 2019 Yamashita, Makinodan, Toritsuka, Yamauchi, Ikawa, Kimoto, Komori, Takada, Kayashima, Hamano-Iwasa, Tsujii, Matsuzaki and Kishimoto. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms