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991.
Both life expectancy and healthy life expectancy in Japan have been increasing and are among the highest in the world, but the gap between them has also been widening. To examine the recent trends in old age disability, chronic medical conditions and mortality in Japan, we retrospectively analyzed three nationally representative datasets: Comprehensive Survey of Living Conditions (2001–2013), Patient Survey (1996–2011) and Vital Statistics (1995–2010). We obtained the sex- and age-stratified trends in disability rate, treatment rates of nine selected chronic medical conditions (cerebrovascular diseases, joint disorders, fractures, osteoporosis, ischemic heart disease, diabetes mellitus, hypertension, pneumonia and malignant neoplasms), total mortality rate and mortality rates from specific causes (cerebrovascular diseases, heart diseases, pneumonia and malignant neoplasms) in both sexes in four age strata (65–69, 70–74, 75–79, 80–84 years). Disability rates declined significantly in both sexes. Treatment rates of all selected medical conditions also decreased significantly, except for fractures in women and pneumonia. Both total mortality rate and cause-specific mortality rates decreased in both sexes. We concluded that the recent decline in disability rates, treatment rates of chronic medical conditions and mortality rates points toward overall improvement in health conditions in adults over the age of 65 years in Japan. Nonetheless, considering the increase in the number of older adults, the absolute number of older adults with disability or chronic medical conditions will continue to increase and challenge medical and long-term care systems. 相似文献
992.
Hiromichi Saino Tomohiro Sugiyabu Go Ueno Masaki Yamamoto Yoshikazu Ishii Masashi Miyano 《PloS one》2015,10(12)
OXA-58 is a class D β-lactamase from the multi-drug resistant Acinetobacter baumannii. We determined the crystal structure of OXA-58 in a novel crystal, and revealed the structure of the substrate-binding cleft in a closed state, distinct from a previously reported OXA-58 crystal structure with the binding cleft in an open state. In the closed state, the movement of three loops (α3–α4, β6–β7, and β8–α10) forms an arch-like architecture over the binding cleft through interaction between the Phe113 residues of α3–α4 and Met225 of β6–β7. This structure suggests the involvement of these flexible loops in OXA-58 substrate binding. In contrast to the mobile loops, the Ω-loop appeared static, including the conserved loop residues and their hydrogen bonds; the pivotal residue Trp169 within the Ω-loop, ζ-carbamic acid of the modified base catalyst residue Lys86, and nucleophilic residue Ser83. The stability of OXA-58 was enhanced concomitant with an increase in the hydrolytic activity catalyzed by NaHCO3-dependent ζ-carbamic acid formation, with an EC50 of 0.34 mM. The W169A mutant enzyme was significantly thermally unstable even in the presence of 100 mM NaHCO3, whereas the S83A mutant was stabilized with NaHCO3-dependent activation. The ζ-carbamic acid was shown to increase not only OXA-58 hydrolytic activity but also OXA-58 stability through the formation of a hydrogen bond network connected to the Ω-loop with Ser83 and Trp169. Thus, the static Ω-loop is important for OXA-58 stability, whereas the mobile loops of the substrate-binding cleft form the basis for accommodation of the various substituents of β-lactam backbone. 相似文献
993.
Tatsuya Takagi Hirohisa Katagiri Yongji Kim Yoshiyuki Suehara Daisuke Kubota Keisuke Akaike Midori Ishii Kenta Mukaihara Taketo Okubo Hideki Murata Mitsuru Takahashi Kazuo Kaneko Tsuyoshi Saito 《PloS one》2015,10(6)
Background
Skeletal metastasis is a common metastatic event for several carcinomas, and the treatment for skeletal metastasis of unknown primary (SMUP) are a critical issue in cancer therapy. Making a diagnosis of the primary site is the most crucial step in the treatment of SMUP; however, the procedures are sometimes difficult and time-consuming, and the primary site often remains unknown. Therefore, to establish optimal diagnostic strategies and elucidate the overall survival rates of SMUP, we conducted this retrospective study.Methods
We retrospectively analyzed the clinical data for 286 SMUP cases from a total of 2,641 patients with skeletal metastases who were treated between 2002 and 2014 at our initiations.Results
The primary sites were identified in 254/286 patients (88.8%), while 32 (11.2%) primary sites were not detected by our diagnostic strategies. Lung cancer was identified in 72 (25.2%) cases, and was the most frequently observed primary lesion. The median survival time of the SMUP patients was 20.0 months, while the median survival times of solitary bone metastasis cases and multi-bone metastasis cases were 39.0 months and 16.0 months, respectively. The median survival times of prostate cancer cases was over 120 months, that of patients with primary lung cancers was 9.0 months and the median survival time of cases who were finally diagnosed with an unknown primary was 11.0 months.Conclusions
We believe that our study would contribute to establishing an optimal strategy for diagnosing the primary site in SMUP patients, and our data provide definite indications for the survival times for different SMUP situations. 相似文献994.
995.
996.
Takayoshi Ishii 《Cell cycle (Georgetown, Tex.)》2014,13(9):1368-1369
997.
Takuo Mizukami Haruka Momose Madoka Kuramitsu Kazuya Takizawa Kumiko Araki Keiko Furuhata Ken J. Ishii Isao Hamaguchi Kazunari Yamaguchi 《PloS one》2014,9(7)
Vaccines are beneficial and universal tools to prevent infectious disease. Thus, safety of vaccines is strictly evaluated in the preclinical phase of trials and every vaccine batch must be tested by the National Control Laboratories according to the guidelines published by each country. Despite many vaccine production platforms and methods, animal testing for safety evaluation is unchanged thus far. We recently developed a systems biological approach to vaccine safety evaluation where identification of specific biomarkers in a rat pre-clinical study evaluated the safety of vaccines for pandemic H5N1 influenza including Irf7, Lgals9, Lgalsbp3, Cxcl11, Timp1, Tap2, Psmb9, Psme1, Tapbp, C2, Csf1, Mx2, Zbp1, Ifrd1, Trafd1, Cxcl9, β2m, Npc1, Ngfr and Ifi47. The current study evaluated whether these 20 biomarkers could evaluate the safety, batch-to-batch and manufacturer-to-manufacturer consistency of seasonal trivalent influenza vaccine using a multiplex gene detection system. When we evaluated the influenza HA vaccine (HAv) from four different manufactures, the biomarker analysis correlated to findings from conventional animal use tests, such as abnormal toxicity test. In addition, sensitivity of toxicity detection and differences in HAvs were higher and more accurate than with conventional methods. Despite a slight decrease in body weight caused by HAv from manufacturer B that was not statistically significant, our results suggest that HAv from manufacturer B is significantly different than the other HAvs tested with regard to Lgals3bp, Tapbp, Lgals9, Irf7 and C2 gene expression in rat lungs. Using the biomarkers confirmed in this study, we predicted batch-to-batch consistency and safety of influenza vaccines within 2 days compared with the conventional safety test, which takes longer. These biomarkers will facilitate the future development of new influenza vaccines and provide an opportunity to develop in vitro methods of evaluating batch-to-batch consistency and vaccine safety as an alternative to animal testing. 相似文献
998.
Motohiko Ukiya Takuma Kawaguchi Kenta Ishii Eri Ogihara Yosuke Tachi Masahiro Kurita Yoichiro Ezaki Makoto Fukatsu Yasunori Kushi Toshihiro Akihisa 《化学与生物多样性》2013,10(7):1260-1268
Nine amino acid conjugate derivatives, each 2 – 10 and 12 – 20 , were prepared from abietic acid ( 1 ) and dehydroabietic acid ( 11 ), respectively, and they were evaluated for their cytotoxicities against four human cancer cell lines, i.e., leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3). All compounds showed cytotoxicities against HL60 with IC50 values in the range of 2.3–37.3 μM . In addition, most of the derivatives exhibited moderate cytotoxicities against the other cancer cell lines. Among the derivatives, methyl N‐[18‐oxoabieta‐8,11,13‐trien‐18‐yl]‐L ‐tyrosinate ( 19 ) exhibited potent cytotoxic activities against four cancer cell lines with IC50 values of 2.3 (HL60), 7.1 (A549), 3.9 (AZ521), and 8.1 μM (SK‐BR‐3). Furthermore, all derivatives were shown to possess high selective cytotoxic activities for leukemia cells, since they exhibited only weak cytotoxicities against normal lymphocyte cell line RPMI1788. 相似文献
999.
Naomichi Abe Tsutomu Nakahara Akane Morita Yoshiko Wada Asami Mori Kenji Sakamoto Tohru Nagamitsu Kunio Ishii 《Birth defects research. Part B, Developmental and reproductive toxicology》2013,98(4):297-303
We previously reported that treatment with KRN633, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, during mid‐pregnancy caused intrauterine growth restriction resulting from impairment of blood vessel growth in the labyrinthine zone of the placenta and fetal organs. However, the relative sensitivities of blood vessels in the placenta and fetal organs to vascular endothelial growth factor (VEGF) inhibitors have not been determined. In this study, we aimed to examine the effects of KRN633 on the vasculatures of organs in mother mice and their newborn pups by immunohistochemical analysis. Pregnant mice were treated daily with KRN633 (5 mg/kg) either from embryonic day 13.5 (E13.5) to E17.5 or from E13.5 to the day of delivery. The weights of the pups of KRN633‐treated mice were lower than those of the pups of vehicle‐treated mothers. However, no significant difference in body weight was observed between the vehicle‐ and KRN633‐treated mice. The vascular development in the organs (the pancreas, kidney, and intestine) and intestinal lymphatic formation of the pups of KRN633‐treated mothers was markedly impaired. In contrast, the KRN633 treatment showed no significant effect on the vascular beds in the organs, including the labyrinthine zone of the placenta, of the mother mice. These results suggest that blood vessels in fetal organs are likely to be more sensitive to reduced VEGF signaling than those in the mother. A partial loss of VEGF function during pregnancy could suppress vascular growth in the fetus without affecting the vasculature in the mother mouse, thereby increasing the risk of intrauterine growth restriction. 相似文献
1000.
Jenny C. Mortimer Xiaolan Yu Sandra Albrecht Francesca Sicilia Mariela Huichalaf Diego Ampuero Louise V. Michaelson Alex M. Murphy Toshiro Matsunaga Samantha Kurz Elaine Stephens Timothy C. Baldwin Tadashi Ishii Johnathan A. Napier Andreas P.M. Weber Michael G. Handford Paul Dupree 《The Plant cell》2013,25(5):1881-1894
The Arabidopsis thaliana protein GOLGI-LOCALIZED NUCLEOTIDE SUGAR TRANSPORTER (GONST1) has been previously identified as a GDP-d-mannose transporter. It has been hypothesized that GONST1 provides precursors for the synthesis of cell wall polysaccharides, such as glucomannan. Here, we show that in vitro GONST1 can transport all four plant GDP-sugars. However, gonst1 mutants have no reduction in glucomannan quantity and show no detectable alterations in other cell wall polysaccharides. By contrast, we show that a class of glycosylated sphingolipids (glycosylinositol phosphoceramides [GIPCs]) contains Man and that this mannosylation is affected in gonst1. GONST1 therefore is a Golgi GDP-sugar transporter that specifically supplies GDP-Man to the Golgi lumen for GIPC synthesis. gonst1 plants have a dwarfed phenotype and a constitutive hypersensitive response with elevated salicylic acid levels. This suggests an unexpected role for GIPC sugar decorations in sphingolipid function and plant defense signaling. Additionally, we discuss these data in the context of substrate channeling within the Golgi. 相似文献