Publications by authors named "Kazuhiko Kobayashi"

94 Publications

Metalloelastase-12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice.

Biomed Rep 2021 Jun 1;14(6):51. Epub 2021 Apr 1.

Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.

Temporomandibular joint dysfunction (TMJD) is characterised by clinical symptoms involving both the masticatory muscles and the temporomandibular joint (TMJ). Disc internal derangement and osteoarthritis (OA) are the most common forms of TMJD. Currently, the molecular process associated with degenerative changes in the TMJ is unclear. Our previous study showed that elastin-digested peptides act on human TMJ synovial cells and lead to upregulation of interleukin-6 (IL-6) and metalloelastase-12 (MMP-12; an elastin-degrading enzyme) . However, there is limited information regarding the involvement of elastin-degradation by MMP-12 in the processes of inflammatory responses and cartilage degradation . STR/Ort mice were used as a model of TMJ OA in the present study. Significant articular cartilage degeneration was observed starting at 20 weeks of age in the STR/Ort mice and this progressed gradually until 40 weeks, compared with the age-matched CBA mice. Immunostaining analysis showed that MMP-12 and IL-6 were expressed in the chondrocytes in the superficial zones of the cartilage. Immunostaining also showed that aggrecanases [a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5] were expressed in the chondrocytes in the superficial zones of the cartilage. These findings suggest that an inflammatory and degradative process was initiated in the TMJ. Harmful mechanical stimuli, particularly pressure, may cause damage to the elastin fibres in the most elastin-rich superficial layer of the articular cartilage. Elastin-digested peptides are then generated as endogenous warning signals and they initiate a pro-inflammatory cascade. This leads to upregulation of pro-inflammatory mediators, such as IL-6 and MMP-12, which further trigger tissue damage resulting in elevated levels of elastin-digested peptides. IL-6 increases expression of the aggrecanases ADAMTS-4 and ADAMTS-5, following cartilage degradation. This leads to the establishment of a positive feedback loop and may result in chronic inflammation and cartilage degradation of the TMJ .
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http://dx.doi.org/10.3892/br.2021.1427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042671PMC
June 2021

Letter to the editor regarding Pleijel et al. 2019: Ozone sensitivity of wheat in different continents - An addendum.

Sci Total Environ 2021 06 12;773:146335. Epub 2021 Mar 12.

The University of Tokyo, Graduate School of Agricultural and Life Sciences, 1-1-1 Yayoi, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.scitotenv.2021.146335DOI Listing
June 2021

Kasumi leukemia cell lines: characterization of tumor genomes with ethnic origin and scales of genomic alterations.

Hum Cell 2020 Jul 16;33(3):868-876. Epub 2020 Mar 16.

Department of Clinical Laboratory, Saitama Cancer Center, Saitama, 362-0806, Japan.

Kasumi-1 has played an important role in an experimental model with t(8;21) translocation, which is a representative example of leukemia cell lines. However, previous studies using Kasumi-1 show discrepancies in the genome profile. The wide use of leukemia cell lines is limited to lines that are well-characterized. The use of additional cell lines extends research to various types of leukemia, and to further explore leukemia pathogenesis, which can be achieved by uncovering the fundamental features of each cell line with accurate data. In this study, ten Kasumi cell lines established in Japan, including five that were previously unknown, have been characterized by SNP microarray and targeted sequencing. SNP genotyping suggested that the genetic ancestry in four of the ten Kasumi cell lines was not classified as Japanese but covered several different east-Asian ethnicities, suggesting that patients in Japan are genetically diverse. TP53 mutations were detected in two cell lines with complex array profiles, indicating chromosomal instability (CIN). A quantitative assessment of tumor genomes at the chromosomal level was newly introduced to reveal total DNA sizes and Scales of Genomic Alterations (SGA) for each cell line. Kasumi-1 and 6 derived from relapsed phases demonstrated high levels of SGA, implying that the level of SGA would reflect on the tumor progression and could serve as an index of CIN. Our results extend the leukemia cellular resources with an additional five cell lines and provide reference genome data with ethnic identities for the ten Kasumi cell lines.
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http://dx.doi.org/10.1007/s13577-020-00347-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324421PMC
July 2020

Quantifying determinants of ozone detoxification by apoplastic ascorbate in peach (Prunus persica) leaves using a model of ozone transport and reaction.

Glob Chang Biol 2020 05 12;26(5):3147-3162. Epub 2020 Apr 12.

Institute of Ecology, Key Laboratory of Agrometeorology of Jiangsu Province, School of Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing, China.

Ascorbate in leaf apoplast (ASC ) reacts with ozone (O ) and thereby reduces O flux reaching plasmalemma (F ). Some studies have shown significant protection of cells from O by ASC , while others have questioned its efficacy. Hypothesizing that the protection by ASC depends on other variables, we quantified determinants of O detoxification with a model of O transport and reaction in apoplast. The model determines ascorbic acid concentration in apoplast (AA ) using measured values of O concentration (c ), leaf tissue ascorbic acid concentration (AA ), cell wall thickness (L ), apoplastic pH (pH ), and stomatal conductance (G ). We compared the measured and model-estimated AA in leaves of peach (Prunus persica) grown in open-top chambers under non-filtered air (NF) and elevated (EO : NF + 80 ppb) O concentrations. The estimated AA in individual leaves agreed well with the measured values (R  = .91). Analyses of the simulation results yielded the following findings: (a) The efficacy of O reduction with ASC as quantified by fractional reduction (ϕ ) of O flux at the surface of plasmalemma (F ) was lowered from 70% in NF to 40% in EO due to the reduction of L . The EO reduced AA , but the lower G and L in EO increased AA resulting in no significant change in AA due to EO . ϕ can be calculated with measured values of AA and L , and F can be estimated with the measurement-based ϕ . (b) When c is increased, F increased curvilinearly with the increase of F : nominal O flux via stomatal diffusion, exhibiting apparent threshold on F . The deviation of F from F became greater when L , pH , and AA were increased. The quantification of ϕ and F using leaf traits shall facilitate the understanding of the mechanisms of differential plant sensitivity to O and improve quantification of the O impacts on plants.
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http://dx.doi.org/10.1111/gcb.15049DOI Listing
May 2020

Water stress rather than N addition mitigates impacts of elevated O on foliar chemical profiles in poplar saplings.

Sci Total Environ 2020 Mar 6;707:135935. Epub 2019 Dec 6.

College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; Institute of Ecology, Key Laboratory of Agrometeorology of Jiangsu Province, School of Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing, 210044, China. Electronic address:

Tropospheric ozone (O) pollution can alter tree chemical profiles, and in turn, affect forest ecosystem function. However, the magnitude of these effects may be modified by variations in soil water and nutrient availability, which makes it difficult to predict the impacts of O in reality. Here we assessed the effects of elevated O alone, and in combination with soil water deficit and N addition, on the phytochemical composition of hybrid poplar (Populus deltoides cv. '55/56' × P. deltoides cv. 'Imperial'). Potted trees were grown in open-top chambers (OTCs) under either charcoal-filtered air or elevated O (non-filtered air +40 ppb of O), and trees within each OTC were grown with four combinations of water (well-watered or water deficit) and nitrogen (with or without N addition) levels. We found that elevated O alone stimulated the accumulation of foliar nitrogen, soluble sugar, and lignin while inhibiting the accumulation of starch, but had limited impacts on condensed tannins and salicinoids in poplar saplings. Graphical vector analysis revealed that these changes in concentrations of nitrogen, starch and lignin were due largely to altered metabolic processes, while increased soluble sugar concentration related mainly to decreased leaf biomass in most cases. The effects of O on poplar foliar chemical profiles depended on soil water, but not soil N, availability. Specifically, O-mediated changes in carbohydrates and lignin were mitigated by decreased soil water content. Taken together, these results suggested that nitrogen acquisition, carbohydrates mobilization and lignification play a role in poplar tolerance to O. Moreover, the impacts of elevated O on phytochemistry of poplar leaves can be context-dependent, with potential consequences for ecosystem processes under future global change scenarios. Our results highlight the needs to consider multi-factors environments to optimize the management of plantations under changing environments.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135935DOI Listing
March 2020

Selectively high efficacy of eribulin against high-grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Oncol Lett 2019 Jun 19;17(6):5064-5072. Epub 2019 Mar 19.

Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.

Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have a poor prognosis. Over the past decade, a major development in the first-line treatment of R/M SCCHN was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy. Currently, a promising novel treatment option in R/M SCCHN has emerged, termed immune checkpoint inhibitors. However, only a few patients presenting with R/M SCCHN have exhibited meaningful tumor regression with these agents. Therefore, novel agents are required to order improve the overall survival of patients with R/M SCCHN. Recently, we demonstrated that R/M SCCHN cells are highly sensitive to eribulin. In the present study, the effects of eribulin, paclitaxel and vinblastine were investigated in R/M SCCHN (OLC-01 and OSC-19) and locally advanced SCCHN (OSC-20) cells. Tumour-inhibitory activities of eribulin against R/M SCCHN were evaluated in orthotopic xenograft models. The data revealed that eribulin has sub-nM growth inhibitory activities against OLC-01 cells, and that it is more potent than paclitaxel and vinblastine. The reduced expression of Tubulin Beta 3 Class III (TUBB3) following treatment was correlated with a high sensitivity to eribulin. Histological analysis of OLC-01 cells in NOD-SCID mice demonstrated that they had a higher invasiveness in the tissue around the alveolar cancer when compared with the histology of OSC-19 cells, which has been reported in our previous study. Treatment with eribulin revealed marked inhibitory activities at 0.125 mg/kg against OLC-01 cells orthotopic xenografts. In conclusion, the results highlight the existence of invasive-type heterogeneity in R/M SCCHN with respect to eribulin sensitivity. Eribulin is already an approved clinical agent; therefore, the continued investigation of its preclinical antitumor attributes may contribute significantly to the future process of identifying novel uses of eribulin against R/M SCCHN.
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http://dx.doi.org/10.3892/ol.2019.10165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507455PMC
June 2019

Isolated pancreatic metastasis from malignant melanoma: a case report and literature review.

Clin J Gastroenterol 2019 Dec 27;12(6):626-636. Epub 2019 May 27.

Department of Endoscopy, Mie University Hospital, Tsu, Mie, Japan.

Isolated pancreatic metastasis from malignant melanoma is rare. Pancreatic metastasis is difficult to diagnose in patients with unknown primary malignant melanoma. Endoscopic ultrasound-guided fine-needle aspiration plays an important role in confirming the diagnosis. A 67-year-old woman was referred to our institution because of a mass in her pancreas. Computed tomography and magnetic resonance imaging revealed a 35-mm mass localized on the pancreatic tail, with low attenuation, surrounded by a high-attenuation rim. Endoscopic ultrasonography revealed a hypoechoic mass with central anechoic areas. Endoscopic ultrasound-guided fine-needle aspiration of the mass was performed, and the pathological diagnosis was malignant melanoma. Intense fluorodeoxyglucose uptake was observed in the pancreatic tail on positron emission tomography-computed tomography. No other malignant melanoma was found. Distal pancreatectomy was performed. Six months postoperatively, positron emission tomography-computed tomography revealed high uptake in the left nasal cavity, and biopsy revealed the mass to be a malignant melanoma, indicating that the primary site of the malignant melanoma was the left nasal cavity and that the pancreatic mass and peritoneal lesion were metastases. The patient had survived > 2 years after the distal pancreatectomy. Pancreatic resection of isolated pancreatic metastasis can possibly prolong survival; however, metastatic melanoma usually has poor prognosis.
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http://dx.doi.org/10.1007/s12328-019-00996-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885028PMC
December 2019

How elevated CO2 affects our nutrition in rice, and how we can deal with it.

PLoS One 2019 5;14(3):e0212840. Epub 2019 Mar 5.

Institute of Crop Sciences, NARO, Tsukuba, Ibaraki, Japan.

Increased concentrations of atmospheric CO2 are predicted to reduce the content of essential elements such as protein, zinc, and iron in C3 grains and legumes, threatening the nutrition of billions of people in the next 50 years. However, this prediction has mostly been limited to grain crops, and moreover, we have little information about either the underlying mechanism or an effective intervention to mitigate these reductions. Here, we present a broader picture of the reductions in elemental content among crops grown under elevated CO2 concentration. By using a new approach, flow analysis of elements, we show that lower absorption and/or translocation to grains is a key factor underlying such elemental changes. On the basis of these findings, we propose two effective interventions-namely, growing C4 instead of C3 crops, and genetic improvements-to minimize the elemental changes in crops, and thereby avoid an impairment of human nutrition under conditions of elevated CO2.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212840PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400444PMC
November 2019

Ozone changes the linear relationship between photosynthesis and stomatal conductance and decreases water use efficiency in rice.

Sci Total Environ 2019 Mar 14;655:1009-1016. Epub 2018 Nov 14.

Faculty of Agriculture, Ibaraki University, Japan.

Ozone is an important air pollutant that affects growth, transpiration, and water use efficiency (WUE) in plants. Integrated models of photosynthesis (A) and stomatal conductance (G) (A-G) are useful tools to consistently assess the impacts of ozone on plant growth, transpiration, and WUE. However, there is no information on how to incorporate the influence of ozone into A-G integrated models for crops. We focused on the Ball-Woodrow-Berry (BWB) relationship, which is a key equation in A-G integrated models, and aimed to address the following questions: (i) how does ozone change the BWB relationship for crops?; (ii) are there any difference in the changes in the BWB relationship among cultivars?, and (iii) how do the changes in the BWB relationship increase or decrease WUE for crops? We grew four rice cultivars in a field under ambient or Free-Air Concentration Enrichment (FACE) of ozone in China and measured A and G using a portable photosynthesis analyzer. We simulated WUE in individual leaves during the ripening period under different BWB relationships. The results showed that ozone significantly changed the BWB relationship only for the most sensitive cultivar, which showed an increase in the intercept of the BWB relationship under FACE conditions. These results imply that changes in the BWB relationship are related to the ozone sensitivity of the cultivar. Simulations of an A-G integrated model showed that increases in the intercept of the BWB relationship from 0.01 to 0.1 mol(HO) m s indicated decreases in WUE by 22%. Since a reduction in WUE indicates increases in water demand per unit of crop growth, air pollution from ozone could be a critical issue in regions where agricultural water is limited, such as in rainfed paddy fields.
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http://dx.doi.org/10.1016/j.scitotenv.2018.11.132DOI Listing
March 2019

Increase of apoplastic ascorbate induced by ozone is insufficient to remove the negative effects in tobacco, soybean and poplar.

Environ Pollut 2019 Feb 10;245:380-388. Epub 2018 Nov 10.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyoku, Tokyo, Japan.

Apoplastic ascorbate (ASC) is an important contributor to the detoxification of ozone (O). The objective of the study is to explore whether ASC is stimulated by elevated O concentrations. The detoxification of O by ASC was quantified in tobacco (Nicotiana L), soybean (Glycine max (L.) Merr.) and poplar (Populus L), which were exposed to charcoal-filtered air (CF) and elevated O treatments (E-O). ASC in the three species were significantly increased by E-O compared with the values in the filtered treatment. For all three species, E-O significantly increased the malondialdehyde (MDA) content and decreased light-saturated rate of photosynthesis (A), suggesting that high O has induced injury/damage to plants. E-O significantly increased redox state in the apoplast (redox state) for all species, whereas no effect on the apoplastic dehydroascorbate (DHA) was observed. In leaf tissues, E-O significantly enhanced reduced-ascorbate (ASC) and total ascorbate (ASC+DHA) in soybean and poplar, but significantly reduced these in tobacco, indicating different antioxidative capacity to the high O levels among the three species. Total antioxidant capacity in the apoplast (TAC) was significantly increased by E-O in tobacco and poplar, but leaf tissue TAC was significantly enhanced only in tobacco. Leaf tissue superoxide anion (O) in poplar and hydrogen peroxide (HO) in tobacco and soybean were significantly increased by E-O. The diurnal variation of ASC, with maximum values occurring in the late morning and lower values experienced in the afternoon, appeared to play an important role in the harmful effects of O on tobacco, soybean and poplar.
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http://dx.doi.org/10.1016/j.envpol.2018.11.030DOI Listing
February 2019

Tropospheric ozone assessment report: Global ozone metrics for climate change, human health, and crop/ecosystem research.

Elementa (Wash D C) 2018 ;1

Dipartimento di Matematica e Fisica, Università Cattolica del Sacro Cuore, Brescia, IT.

Assessment of spatial and temporal variation in the impacts of ozone on human health, vegetation, and climate requires appropriate metrics. A key component of the is the consistent calculation of these metrics at thousands of monitoring sites globally. Investigating temporal trends in these metrics required that the same statistical methods be applied across these ozone monitoring sites. The nonparametric Mann-Kendall test (for significant trends) and the Theil-Sen estimator (for estimating the magnitude of trend) were selected to provide robust methods across all sites. This paper provides the scientific underpinnings necessary to better understand the implications of and rationale for selecting a specific TOAR metric for assessing spatial and temporal variation in ozone for a particular impact. The rationale and underlying research evidence that influence the derivation of specific metrics are given. The form of 25 metrics (4 for model-measurement comparison, 5 for characterization of ozone in the free troposphere, 11 for human health impacts, and 5 for vegetation impacts) are described. Finally, this study categorizes health and vegetation exposure metrics based on the extent to which they are determined only by the highest hourly ozone levels, or by a wider range of values. The magnitude of the metrics is influenced by both the distribution of hourly average ozone concentrations at a site location, and the extent to which a particular metric is determined by relatively low, moderate, and high hourly ozone levels. Hence, for the same ozone time series, changes in the distribution of ozone concentrations can result in different changes in the magnitude and direction of trends for different metrics. Thus, dissimilar conclusions about the effect of changes in the drivers of ozone variability (e.g., precursor emissions) on health and vegetation exposure can result from the selection of different metrics.
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http://dx.doi.org/10.1525/elementa.279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6192432PMC
January 2018

Closing the global ozone yield gap: Quantification and cobenefits for multistress tolerance.

Glob Chang Biol 2018 10 7;24(10):4869-4893. Epub 2018 Aug 7.

Department of Botany, Institute of Science, Banaras Hindu University, Uttar Pradesh, India.

Increasing both crop productivity and the tolerance of crops to abiotic and biotic stresses is a major challenge for global food security in our rapidly changing climate. For the first time, we show how the spatial variation and severity of tropospheric ozone effects on yield compare with effects of other stresses on a global scale, and discuss mitigating actions against the negative effects of ozone. We show that the sensitivity to ozone declines in the order soybean > wheat > maize > rice, with genotypic variation in response being most pronounced for soybean and rice. Based on stomatal uptake, we estimate that ozone (mean of 2010-2012) reduces global yield annually by 12.4%, 7.1%, 4.4% and 6.1% for soybean, wheat, rice and maize, respectively (the "ozone yield gaps"), adding up to 227 Tg of lost yield. Our modelling shows that the highest ozone-induced production losses for soybean are in North and South America whilst for wheat they are in India and China, for rice in parts of India, Bangladesh, China and Indonesia, and for maize in China and the United States. Crucially, we also show that the same areas are often also at risk of high losses from pests and diseases, heat stress and to a lesser extent aridity and nutrient stress. In a solution-focussed analysis of these results, we provide a crop ideotype with tolerance of multiple stresses (including ozone) and describe how ozone effects could be included in crop breeding programmes. We also discuss altered crop management approaches that could be applied to reduce ozone impacts in the shorter term. Given the severity of ozone effects on staple food crops in areas of the world that are also challenged by other stresses, we recommend increased attention to the benefits that could be gained from addressing the ozone yield gap.
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http://dx.doi.org/10.1111/gcb.14381DOI Listing
October 2018

Carbon dioxide (CO) levels this century will alter the protein, micronutrients, and vitamin content of rice grains with potential health consequences for the poorest rice-dependent countries.

Sci Adv 2018 05 23;4(5):eaaq1012. Epub 2018 May 23.

USDA-ARS, Adaptive Cropping Systems Laboratory, Beltsville, MD 20705, USA.

Declines of protein and minerals essential for humans, including iron and zinc, have been reported for crops in response to rising atmospheric carbon dioxide concentration, [CO]. For the current century, estimates of the potential human health impact of these declines range from 138 million to 1.4 billion, depending on the nutrient. However, changes in plant-based vitamin content in response to [CO] have not been elucidated. Inclusion of vitamin information would substantially improve estimates of health risks. Among crop species, rice is the primary food source for more than 2 billion people. We used multiyear, multilocation in situ FACE (free-air CO enrichment) experiments for 18 genetically diverse rice lines, including Japonica, Indica, and hybrids currently grown throughout Asia. We report for the first time the integrated nutritional impact of those changes (protein, micronutrients, and vitamins) for the 10 countries that consume the most rice as part of their daily caloric supply. Whereas our results confirm the declines in protein, iron, and zinc, we also find consistent declines in vitamins B1, B2, B5, and B9 and, conversely, an increase in vitamin E. A strong correlation between the impacts of elevated [CO] on vitamin content based on the molecular fraction of nitrogen within the vitamin was observed. Finally, potential health risks associated with anticipated CO-induced deficits of protein, minerals, and vitamins in rice were correlated to the lowest overall gross domestic product per capita for the highest rice-consuming countries, suggesting potential consequences for a global population of approximately 600 million.
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http://dx.doi.org/10.1126/sciadv.aaq1012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966189PMC
May 2018

Ozone pollution will compromise efforts to increase global wheat production.

Glob Chang Biol 2018 08 16;24(8):3560-3574. Epub 2018 May 16.

European Commission, Joint Research Centre, Ispra, Italy.

Introduction of high-performing crop cultivars and crop/soil water management practices that increase the stomatal uptake of carbon dioxide and photosynthesis will be instrumental in realizing the United Nations Sustainable Development Goal (SDG) of achieving food security. To date, however, global assessments of how to increase crop yield have failed to consider the negative effects of tropospheric ozone, a gaseous pollutant that enters the leaf stomatal pores of plants along with carbon dioxide, and is increasing in concentration globally, particularly in rapidly developing countries. Earlier studies have simply estimated that the largest effects are in the areas with the highest ozone concentrations. Using a modelling method that accounts for the effects of soil moisture deficit and meteorological factors on the stomatal uptake of ozone, we show for the first time that ozone impacts on wheat yield are particularly large in humid rain-fed and irrigated areas of major wheat-producing countries (e.g. United States, France, India, China and Russia). Averaged over 2010-2012, we estimate that ozone reduces wheat yields by a mean 9.9% in the northern hemisphere and 6.2% in the southern hemisphere, corresponding to some 85 Tg (million tonnes) of lost grain. Total production losses in developing countries receiving Official Development Assistance are 50% higher than those in developed countries, potentially reducing the possibility of achieving UN SDG2. Crucially, our analysis shows that ozone could reduce the potential yield benefits of increasing irrigation usage in response to climate change because added irrigation increases the uptake and subsequent negative effects of the pollutant. We show that mitigation of air pollution in a changing climate could play a vital role in achieving the above-mentioned UN SDG, while also contributing to other SDGs related to human health and well-being, ecosystems and climate change.
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http://dx.doi.org/10.1111/gcb.14157DOI Listing
August 2018

Comparison of crop yield sensitivity to ozone between open-top chamber and free-air experiments.

Glob Chang Biol 2018 06 24;24(6):2231-2238. Epub 2018 Feb 24.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Assessments of the impacts of ozone (O ) on regional and global food production are currently based on results from experiments using open-top chambers (OTCs). However, there are concerns that these impact estimates might be biased due to the environmental artifacts imposed by this enclosure system. In this study, we collated O exposure and yield data for three major crop species-wheat, rice, and soybean-for which O experiments have been conducted with OTCs as well as the ecologically more realistic free-air O elevation (O -FACE) exposure system; both within the same cultivation region and country. For all three crops, we found that the sensitivity of crop yield to the O metric AOT40 (accumulated hourly O exposure above a cut-off threshold concentration of 40 ppb) significantly differed between OTC and O -FACE experiments. In wheat and rice, O sensitivity was higher in O -FACE than OTC experiments, while the opposite was the case for soybean. In all three crops, these differences could be linked to factors influencing stomatal conductance (manipulation of water inputs, passive chamber warming, and cultivar differences in gas exchange). Our study thus highlights the importance of accounting for factors that control stomatal O flux when applying experimental data to assess O impacts on crops at large spatial scales.
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http://dx.doi.org/10.1111/gcb.14077DOI Listing
June 2018

Temporal trends in arthropod abundances after the transition to organic farming in paddy fields.

PLoS One 2018 11;13(1):e0190946. Epub 2018 Jan 11.

Laboratory of Biodiversity Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Organic farming aims to reduce the effect on the ecosystem and enhance biodiversity in agricultural areas, but the long-term effectiveness of its application is unclear. Assessments have rarely included various taxonomic groups with different ecological and economic roles. In paddy fields with different numbers of years elapsed since the transition from conventional to organic farming, we investigated changes in the abundance of insect pests, generalist predators, and species of conservation concern. The abundance of various arthropods exhibited diverse trends with respect to years elapsed since the transition to organic farming. Larval lepidopterans, Tetragnatha spiders, and some planthoppers and stink bugs showed non-linear increases over time, eventually reaching saturation, such as the abundance increasing for several years and then becoming stable after 10 years. This pattern can be explained by the effects of residual pesticides, the lag time of soil mineralization, and dispersal limitation. A damselfly (Ischnura asiatica) did not show a particular trend over time, probably due to its rapid immigration from source habitats. Unexpectedly, both planthoppers and some leafhoppers exhibited gradual decreases over time. As their abundances were negatively related to the abundance of Tetragnatha spiders, increased predation by natural enemies might gradually decrease these insect populations. These results suggest that the consideration of time-dependent responses of organisms is essential for the evaluation of the costs and benefits of organic farming, and such evaluations could provide a basis for guidelines regarding the length of time for organic farming to restore biodiversity or the economic subsidy needed to compensate for pest damage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190946PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764318PMC
February 2018

Long-Term Outcomes of 107 Cases of Primary Thyroid Mucosa-Associated Lymphoid Tissue Lymphoma at a Single Medical Institution in Japan.

J Clin Endocrinol Metab 2018 02;103(2):732-739

Ito Hospital, Tokyo, Japan.

Context: Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis.

Objective: To provide information on long-term outcomes that would facilitate establishment of the optimal management strategy for thyroid lymphoma.

Design, Setting, And Participants: Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed.

Main Outcome Measure: Overall and event-free survival (EFS).

Results: Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% [95% confidence interval (CI), 87% to 97%] and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively.

Conclusions: Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities.
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http://dx.doi.org/10.1210/jc.2017-01478DOI Listing
February 2018

Successful endoscopic treatment for gastric mural abscess due to fish bone migration.

Ann Gastroenterol 2017 14;30(6):697. Epub 2017 Jul 14.

Department of Gastroenterology, Matsusaka Central Hospital, Matsusaka (Masabumi Kaneko, Hiroaki Naota, Kazuhiko Kobayashi), Japan.

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http://dx.doi.org/10.20524/aog.2017.0177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670291PMC
July 2017

Ozone exposure- and flux-based response relationships with photosynthesis of winter wheat under fully open air condition.

Sci Total Environ 2018 Apr 18;619-620:1538-1544. Epub 2017 Oct 18.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Five winter wheat cultivars were exposed to ambient (A-O) and elevated (E-O, 1.5 ambient) O in a fully open-air fumigation system in China. Ozone exposure- and flux based response relationships were established for seven physiological variables related to photosynthesis. The performance of the fitting of the regressions in terms of R increased when second order regressions instead of first order ones were used, suggesting that effects of O were more pronounced towards the last developmental stages of the wheat. The more robust indicators were those related with CO assimilation, Rubisco activity and RuBP regeneration capacity (A, J and Vc), and chlorophyll content (Chl). Flux-based metrics (POD, Phytotoxic O Dose over a threshold ynmolOms) predicted slightly better the responses to O than exposure metrics (AOTX, Accumulated O exposure over an hourly Threshold of X ppb) for most of the variables. The best performance was observed for metrics PODA, J and Vc) and POD (Chl). For this crop, the proposed response functions could be used for O risk assessment based on physiological effects and also to include the influence of O on yield or other variables in models with a photosynthetic component.
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http://dx.doi.org/10.1016/j.scitotenv.2017.10.089DOI Listing
April 2018

An Unusual Lesion in the Ascending Colon.

Gastroenterology 2018 Jun 23;154(8):2037-2038. Epub 2017 Sep 23.

Department of Gastroenterology, Matsusaka Central Hospital, Matsusaka, Japan.

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http://dx.doi.org/10.1053/j.gastro.2017.09.015DOI Listing
June 2018

Elastin‑derived peptides are involved in the processes of human temporomandibular disorder by inducing inflammatory responses in synovial cells.

Mol Med Rep 2017 Sep 15;16(3):3147-3154. Epub 2017 Jul 15.

Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920‑8640, Japan.

Temporomandibular joint dysfunction (TMD) is a collection of clinical symptoms that involve masticatory muscles and the temporomandibular joint (TMJ). Common symptoms include limited jaw motion and joint sound/pain, along with TMJ disc displacement. TMD is frequently associated with synovitis, a chronic inflammation of the synovium. Fibroblast‑like synovial cells have been identified to produce several inflammatory mediators and may have an important role in the progression of TMJ inflammation. Degradation of the extracellular matrix molecule elastin may lead to the release of bioactive peptides. The present study aimed to explore the role of elastin‑derived peptides (EDPs) in human temporomandibular disorders. Therefore, interleukin‑6 (IL‑6) expression in the synovial fluid obtained from patients with TMD correlated significantly with two clinical parameters, specifically TMJ locking and pain/jaw function on a visual analog scale (VAS). To the best of our knowledge, this is the first study to determine that the concentration of EDPs in synovial fluid from patients with TMD may also be significantly correlated with the duration of TMJ locking, the VAS score and IL‑6 expression. In vitro, EDPs act on human TMJ synovial cells to promote upregulation of IL‑6 and the elastin‑degrading enzyme matrix metalloproteinase‑12 (MMP‑12). The upregulation of IL‑6 and MMP‑12 expression by EDPs may be mediated through elastin‑binding proteins (EBP) and a protein kinase A signalling cascade. These findings suggest a model for inflammation in the TMJ where EDPs are generated by harmful mechanical stimuli, induce both a pro‑inflammatory cascade and increase expression of MMP‑12 through activation of the EBP signalling cascade. This may lead to further increases in EDP levels, establishing a positive feedback loop leading to chronic inflammation in the TMJ. Therefore, significantly elevated levels of EDPs and IL‑6 in the synovial fluid of the TMJ may be indicators of the pathological conditions of the joint.
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http://dx.doi.org/10.3892/mmr.2017.7012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548023PMC
September 2017

Evaluation of an e-learning system for diagnosis of gastric lesions using magnifying narrow-band imaging: a multicenter randomized controlled study.

Endoscopy 2017 Oct 21;49(10):957-967. Epub 2017 Jun 21.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

 Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness.  This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored < 80 % accuracy on Test 1. The primary end point was the difference in accuracy between Test 1 and Test 2 for the two groups. A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9 % for the e-learning group and 61.7 % for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively;  < 0.001). This study clearly demonstrated the efficacy of the e-learning system in improving practitioners' capabilities to diagnose EGC using M-NBI.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000008569).
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http://dx.doi.org/10.1055/s-0043-111888DOI Listing
October 2017

A Long Surviving Case with Undifferentiated Pancreatic Carcinoma.

Intern Med 2016;55(22):3403-3404. Epub 2016 Nov 15.

Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Japan.

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http://dx.doi.org/10.2169/internalmedicine.55.6877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5173517PMC
November 2016

Differential effects of ozone on photosynthesis of winter wheat among cultivars depend on antioxidative enzymes rather than stomatal conductance.

Sci Total Environ 2016 Dec 17;572:404-411. Epub 2016 Aug 17.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Five modern cultivars of winter wheat (Triticum aestivum L.): Yangmai16 (Y16), Yangmai 15 (Y15), Yangfumai 2 (Y2), Yannong 19 (Y19) and Jiaxing 002 (J2) were investigated to determine the impacts of elevated ozone concentration (E-O) on photosynthesis-related parameters and the antioxidant system under fully open-air field conditions in China. The plants were exposed to E-O at 1.5 times the ambient ozone concentration (A-O) from the initiation of tillering to final harvest. Pigments, gas exchange rates, chlorophyll a fluorescence, antioxidants contents, antioxidative enzyme activity and lipid oxidation were measured in three replicated plots throughout flag leaf development. Results showed that significant O effects on most variables were only found during the mid-grain filling stage. Across five cultivars, E-O significantly accelerated leaf senescence, as indicated by increased lipid oxidation as well as faster declines in pigment amounts and photosynthetic rates. The lower photosynthetic rates were mainly due to non-stomatal factors, e.g. lower maximum carboxylation capacity and electron transport rates. There were strong interactions between O and cultivar in photosynthetic pigments, light-saturated photosynthesis rate and chlorophyll a fluorescence with O-sensitive (Y19, Y2 and Y15) and O-tolerant (J2, Y16) cultivars being clearly differentiated in their responses to E-O. E-O significantly influenced the antioxidative enzymes but not antioxidant contents. Significant interactions between O and cultivar were found in antioxidative enzymes, such as SOD and CAT, but not in stomatal conductance (g). Therefore, it can be concluded that antioxidative enzymes rather than g or antioxidants are responsible for the differential responses to E-O among cultivars. These findings provide important information for the development of accurate modeling O effects on crops, especially with respect to the developmental stage when O damage to photosynthesis becomes manifest.
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http://dx.doi.org/10.1016/j.scitotenv.2016.08.083DOI Listing
December 2016

Impact of the automatic rounding-off function of the computerized physician order entry system on the ordering time and dose dispersion of chemotherapeutic drugs in regimens for hematologic malignancies.

Int J Med Inform 2016 Jan 24;85(1):76-9. Epub 2015 Oct 24.

Division of Hematology, Teikyo University Chiba Medical Center, Ichihara, Japan.

Introduction: EGMAIN-GX is the computerized physician order entry system used in Japan. The automatic rounding-off of the calculated dose of chemotherapeutic drugs is an update in version 4, compared to version 2. We conducted a comparative study between EGMAIN-GX versions 2 and 4 to estimate the effect of the automatic rounding-off function on ordering time and dose dispersion.

Methods: Twelve hematologists ordered 5 predefined chemotherapeutic regimens most commonly used in treating hematologic malignancies, twice for each regimen.

Results: EGMAIN-GX version 4 significantly reduced ordering times compared to version 2 (635s vs. 259s, p<0.01). EGMAIN-GX version 4 also yielded a significantly higher ratio of actual to ideal doses of chemotherapeutic drugs than did version 2 (1.0097 and 0.9997, respectively; p<0.01) and a lower standard deviation (0.0275 and 0.0290, respectively).

Conclusions: The automatic rounding-off function could decrease the ordering time and dose dispersion of chemotherapeutic drugs.
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http://dx.doi.org/10.1016/j.ijmedinf.2015.10.006DOI Listing
January 2016

Diurnal variation of apoplastic ascorbate in winter wheat leaves in relation to ozone detoxification.

Environ Pollut 2015 Dec 2;207:413-9. Epub 2015 Nov 2.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

Besides stomatal closure, biological detoxification is an important protection mechanism for plants against ozone (O3). This study investigated the diurnal changes of ascorbate (a major detoxification agent) in the apoplast and leaf tissues of winter wheat grown under ambient air field conditions. Results showed the reduced ascorbate in the apoplast (ASCapo) exhibited a peak in late morning or midday, mismatching with either the maximum external O3 concentrations in mid-afternoon or the maximum stomatal O3 uptake between late morning and mid-afternoon. In contrast, the ASC in leaf tissues remained stable throughout the day. The investigations conducted in a Free-Air Concentration Elevation of O3 system confirmed that the diurnal variations of the ASCapo were induced more by the daily variations of O3 concentrations rather than the cumulative O3 effects. In conclusion, the O3-stress detoxification should be a dynamic variable rather than a fixed threshold as assumed in the stomatal flux-based O3 dose metrics.
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http://dx.doi.org/10.1016/j.envpol.2015.09.040DOI Listing
December 2015

Diagnostic Accuracy on Magnetic Resonance Imaging for the Diagnosis of Osteoarthritis of the Temporomandibular Joint.

J Clin Diagn Res 2015 Jul 1;9(7):ZC95-7. Epub 2015 Jul 1.

DMD, Department of Oral and Maxillofacial Surgery, Tonami General Hospital , Japan .

Objectives: Osteoarthritis, which is also called degenerative arthritis or degenerative joint disease, is primarily a disease that results from the breakdown and loss of cartilage in joints. The purpose of this study was to investigate the diagnostic accuracy of magnetic resonance images for the diagnosis of osteoarthritis of the temporomandibular joint.

Materials And Methods: Fifty patients (50 joints) with closed locking of the temporomandibular joint were examined with magnetic resonance imaging and then underwent arthroscopic surgery. The agreement of osteoarthritis between magnetic resonance images and arthroscopic findings was studied using the κ coefficient.

Results: The incidence of osteoarthritis on magnetic resonance images (38%) was significantly lower than that in arthroscopic findings (78%). There was no significant agreement between these two findings (p=.108). The κ coefficient was 0.154.

Conclusion: The diagnostic accuracy of magnetic resonance images for osteoarthritis of the temporomandibular joint was low; early osteoarthritis could not be diagnosed from magnetic resonance images. Clinicians should understand that the diagnostic accuracy of osteoarthritis without arthroscopy is not always high.
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http://dx.doi.org/10.7860/JCDR/2015/12302.6260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573048PMC
July 2015

Effectiveness of electric toothbrushing in patients with neuromuscular disability: A randomized observer-blind crossover trial.

Spec Care Dentist 2016 Jan 21;36(1):13-7. Epub 2015 Sep 21.

Department of Dentistry, National Hospital Organization Iou Hospital, Kanazawa, Japan.

Objective: To evaluate the effectiveness of an electric toothbrush for oral care in patients with neuromuscular disability.

Methods: In this randomized observer-blind crossover trial, 30 patients with neuromuscular disease performed either electric or manual toothbrushing each for 4 weeks. Plaque status (plaque control record), periodontal pocket depth, oral status (oral assessment guide), salivary bacterial count, and toothbrushing time were assessed after each period and compared between the two groups by Wilcoxon signed-rank test.

Results: Twenty-eight patients completed the study, including 18 communicative patients. Periodontal pockets were significantly shallower and toothbrushing time was significantly shorter with electric toothbrush use than with manual toothbrush use. No significant differences in oral status and salivary bacterial counts were noted between the approaches, but plaque status significantly improved after electric toothbrushing in communicative patients.

Conclusions: Electric toothbrushing is beneficial for maintaining oral health in patients with neuromuscular disability and reducing the caregivers' oral care burden.
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http://dx.doi.org/10.1111/scd.12141DOI Listing
January 2016

Constraints to nitrogen acquisition of terrestrial plants under elevated CO2.

Glob Chang Biol 2015 Aug 19;21(8):3152-68. Epub 2015 May 19.

Department of Biological and Environmental Sciences, University of Gothenburg, P.O. Box 461, 405 30, Gothenburg, Sweden.

A key part of the uncertainty in terrestrial feedbacks on climate change is related to how and to what extent nitrogen (N) availability constrains the stimulation of terrestrial productivity by elevated CO2 (eCO2 ), and whether or not this constraint will become stronger over time. We explored the ecosystem-scale relationship between responses of plant productivity and N acquisition to eCO2 in free-air CO2 enrichment (FACE) experiments in grassland, cropland and forest ecosystems and found that: (i) in all three ecosystem types, this relationship was positive, linear and strong (r(2) = 0.68), but exhibited a negative intercept such that plant N acquisition was decreased by 10% when eCO2 caused neutral or modest changes in productivity. As the ecosystems were markedly N limited, plants with minimal productivity responses to eCO2 likely acquired less N than ambient CO2 -grown counterparts because access was decreased, and not because demand was lower. (ii) Plant N concentration was lower under eCO2 , and this decrease was independent of the presence or magnitude of eCO2 -induced productivity enhancement, refuting the long-held hypothesis that this effect results from growth dilution. (iii) Effects of eCO2 on productivity and N acquisition did not diminish over time, while the typical eCO2 -induced decrease in plant N concentration did. Our results suggest that, at the decennial timescale covered by FACE studies, N limitation of eCO2 -induced terrestrial productivity enhancement is associated with negative effects of eCO2 on plant N acquisition rather than with growth dilution of plant N or processes leading to progressive N limitation.
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http://dx.doi.org/10.1111/gcb.12938DOI Listing
August 2015