109 results on '"Iijima, K"'
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2. Epitaxial growth and dielectric properties of BaTiO3 films on Pt electrodes by reactive evaporation.
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Yano, Y., Iijima, K., Daitoh, Y., Terashima, T., Bando, Y., Watanabe, Y., Kasatani, H., and Terauchi, H.
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EPITAXY , *ELECTRODES , *DIELECTRICS - Abstract
Presents a study which performed the epitaxial growth and examined the dielectric properties of BaTiO[sub3] films on plutonium electrodes by reactive evaporation. Experimental details; Results and discussion; Conclusion.
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- 1994
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3. Identification of a high-risk group for low-dose aspirin-induced gastropathy by measuring serum pepsinogen in H. pylori-infected subjects.
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Iijima, K., Koike, T., Ara, N., Nakagawa, K., Kondo, Y., Uno, K., Hatta, W., Asano, N., Imatani, A., and Shimosegawa, T.
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GASTRIC diseases , *GASTRIC mucosa , *HELICOBACTER pylori infections , *ASPIRIN , *PEPSINOGEN , *SERUM , *DISEASE risk factors , *DISEASES - Abstract
Background: We recently demonstrated in humans that the extent of low-dose aspirin (LDA)-induced gastropathy was directly related to the individual gastric acid secretion level. We also established reliable cutoff serum pepsinogen (PG) values to predict gastric acid secretion status. In this study, we investigated the clinical usefulness of measuring the serum pepsinogen values for identifying a high-risk group for gastric mucosal injury among chronic LDA users. Methods: One hundred long-term LDA users were enrolled in this analysis. Serum from each subject was subjected to determination of H. pylori status and measurement of pepsinogen values. According to our recent report, a PG I value ≥ 50 ng/mL was defined as estimated hyperchlorhydria in H. pylori-negative subjects, while a PG I/II ≥ 3.3 was defined as estimated hyperchlorhydria in H. pylori-positive subjects. The grade of gastric mucosal injury was assessed endoscopically, and multiple logistic regression analyses were used to estimate the risk. Results: Estimated hyperchlorhydria was a strong independent risk for intensive gastric mucosal injury with an OR (95 % CI): 34.0 (4.5-259) and for gastric ulcer with an OR (95 % CI): 10.2 (1.8-58.3) in H. pylori-positive subjects, while it was not a significant risk in H. pylori-negative subjects. The association persisted even after excluding those with conventional risks for LDA-gastropathy such as ulcer histories. Conclusion: Using simple serum measurement of H. pylori antibody and pepsinogen concentrations, an extremely high-risk group for LDA-induced gastropathy could be extracted, and these patients should become a therapeutic target for prevention of LDA-induced gastropathy. [ABSTRACT FROM AUTHOR]
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- 2015
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4. Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice.
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Drake, L. Y., Iijima, K., and Kita, H.
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NATURAL immunity , *IMMUNE response , *LABORATORY mice , *CYTOKINES , *PATHOPHYSIOLOGY of asthma - Abstract
Background Innate lymphoid cells ( ILCs) play important roles in innate immunity and tissue remodeling via production of various cytokines and growth factors. Group 2 ILCs ( ILC2s) were recently shown to mediate the immune pathology of asthma even without adaptive immunity. However, little is known about possible interactions between ILC2s and other immune cells. We sought to investigate the capacity of ILC2s to regulate effector functions of T cells. Methods We isolated ILC2s from the lungs of naïve mice. We cultured CD4+ T cells with ILC2s in vitro and examined the functions of these cell types. The mechanisms were investigated using blocking antibodies and cells isolated from cytokine-deficient mice. For the in vivo study, we adoptively transferred ILC2s and CD4+ T cells into Il7ra −/− mice and subsequently exposed the mice to ovalbumin and a cysteine protease. Results Lung ILC2s enhanced CD4+ T-cell proliferation and promoted production of type 2 cytokines in vitro. The interaction between ILC2s and CD4+ T cells involved costimulatory molecule OX40L and cytokine IL-4, which was mainly derived from ILC2s. Adoptive transfer of both ILC2 and CD4+ T-cell populations, but not each population alone, into Il7ra −/− mice resulted in induction of a robust antigen-specific type 2 cytokine response and airway inflammation. Conclusion Lung ILC2s function to promote adaptive immunity in addition to their established roles in innate immunity. This novel function of ILC2s needs to be taken into account when considering the pathophysiology of asthma and other allergic airway diseases. [ABSTRACT FROM AUTHOR]
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- 2014
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5. Reactive Increase in Gastric Mucus Secretion Is an Adaptive Defense Mechanism Against Low-Dose Aspirin-Induced Gastropathy.
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Iijima, K., Iwabuchi, T., Ara, N., Koike, T., Shinkai, H., Kamata, Y., Ichikawa, T., Ishihara, K., and Shimosegawa, T.
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GASTRIC mucosa , *GASTRIC diseases , *ASPIRIN , *HELICOBACTER pylori , *DRUG dosage , *ENDOSCOPIC surgery , *THERAPEUTICS - Abstract
Background: Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. Aim: To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. Methods: Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. Results: Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min ( P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) ( P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ('severe gastropathy' vs. 'modest gastropathy') revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. Conclusions: The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications. [ABSTRACT FROM AUTHOR]
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- 2013
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6. Association of gastric acid and mucus secretion level with low-dose aspirin-induced gastropathy.
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Iijima K, Ara N, Abe Y, Koike T, Iwai W, Iwabuchi T, Ichikawa T, Kamata Y, Ishihara K, and Shimosegawa T
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BACKGROUND: Low-dose aspirin is known to cause upper gastrointestinal complications. The mechanism by which the aspirin disrupts gastric mucosal integrity remains to be clarified. In this study we investigated the temporal association of gastric secretory parameters (acid and mucus) with aspirin-induced gastropathy. METHODS: In 42 long-term low-dose aspirin-takers and the same number of sex- and age-matched controls, pentagastrin-stimulated gastric juice was collected for 10 min during endoscopic examination. The collected gastric juice was divided and half was submitted to analysis for gastric acid (mEq/10 min) and the other half was analyzed for mucin (mg hexose/10 min) output. The grade of gastric mucosal injury was assessed endoscopically according to the modified Lanza score, and a score of more than 4 was defined as the presence of severe gastropathy. RESULTS: While gastric acid secretion did not differ significantly between aspirin-takers and controls, gastric mucus secretion, in terms of mucin output, was significantly increased in aspirin-takers compared to controls (4.1 (SD 4.8) vs. 2.3 (1.4) mg hexose/10 min, P < 0.05). Consequently, the acid/mucin ratio was significantly decreased in aspirin-takers compared to controls (1.2 (1.0) vs. 1.7 (1.4), P < 0.05). In the subanalysis of 25 aspirin-takers without severe gastropathy, gastric mucus secretion was increased and the acid/mucus ratio was decreased compared with controls, but there was no such association in the remaining 17 aspirin-takers with severe gastropathy. CONCLUSION: Overall, gastric mucus secretion is increased in aspirin-takers, suggesting a functional adaptive response to long-term administration of the drug. However, it is possible that the adaptive response is impaired in some aspirin takers, who might be susceptible to severe upper gastrointestinal complication. [ABSTRACT FROM AUTHOR]
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- 2012
7. Construction and evaluation of self-cloning bottom-fermenting yeast with high SSU1 expression K. Iijima and T. Ogata Construction of self-cloning brewer's yeast.
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Iijima, K. and Ogata, T.
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YEAST , *BREWING , *SULFUR compounds , *FERMENTATION , *DNA - Abstract
To construct a self-cloning brewer's yeast that can minimize the unfavourable flavours caused by oxidation and certain kinds of sulfur compounds. DNA fragments of a high-expression promoter from the TDH3 gene originating from Saccharomyces cerevisiae were integrated into the promoter regions of the S. cerevisiae-type and Saccharomyces bayanus-type SSU1 genes of bottom-fermenting brewer's yeast. PCR and sequencing confirmed the TDH3 promoter was correctly introduced into the SSU1 regions of the constructed yeasts, and no foreign DNA sequences were found. Using the constructed yeasts, the concentration of sulfite in fermenting wort was higher when compared with the parent strain. In addition, the concentrations of hydrogen sulfide, 3-methyl-2-buten-1-thiol (MBT) and 2-mercapto-3-methyl-1-butanol (2M3MB) were lower when compared with the parent strain. We successfully constructed a self-cloning brewer's yeast with high SSU1 expression that enhanced the sulfite-excreting ability and diminished the production ability of hydrogen sulfide, MBT and 2M3MB. The self-cloning brewer's yeast with high SSU1 expression would contribute to the production of superior quality beer with a high concentration of sulfite and low concentrations of hydrogen sulfide, MBT and 2M3MB. [ABSTRACT FROM AUTHOR]
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- 2010
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8. Gastric hyposecretion in esophageal squamous-cell carcinomas.
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Iijima, K., Koike, T., Abe, Y., Yamagishi, H., Ara, N., Asanuma, K., Uno, K., Imatani, A., Nakaya, N., Ohara, S., and Shimosegawa, T.
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SQUAMOUS cell carcinoma , *STOMACH cancer , *GASTRIC acid , *ATROPHY , *PYLORIC spasms , *BIOPSY , *ENZYMES , *ESOPHAGEAL tumors , *HELICOBACTER diseases , *HELICOBACTER pylori , *LONGITUDINAL method , *REGRESSION analysis , *LOGISTIC regression analysis , *CASE-control method , *ENDOSCOPIC gastrointestinal surgery , *ATROPHIC gastritis , *DISEASE complications - Abstract
Recently, gastric fundic atrophy is reported to be an independent risk factor for esophageal squamous-cell carcinoma (ESCC). The aim of this study is to investigate the acid secretory level in ESCC in a case-control study. From April 2004 to March 2008, 100 consecutive subjects with early ESCC and 100 age- and sex-matched asymptomatic controls were prospectively enrolled. Gastrin-stimulated acid output was assessed by endoscopic gastrin test. Conditional regression analyses were used to adjust for other potential confounders. Multivariate analyses revealed a strong association between profound hypochlorhydria and ESCC with odds ratio (95% confidence interval): 6.0 (1.9-18.4). The association remained significant after adjusting for the effect of gastric atrophy as a covariate. The association became stronger as the ESCC developed more distal site of the esophagus. This study indicates that profound hypochlorhydria is a strong independent risk factor for ESCC even after adjusting for the influence of gastric atrophy. [ABSTRACT FROM AUTHOR]
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- 2010
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9. Reactive nitrogen oxide species induce dilatation of the intercellular space of rat esophagus.
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Ito, H., Iijima, K., Ara, N., Asanuma, K., Endo, H., Asano, N., Koike, T., Abe, Y., Imatani, A., and Shimosegawa, T.
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NITRIC oxide , *EPITHELIUM , *GASTROESOPHAGEAL reflux , *GASTRIC acid , *TRANSMISSION electron microscopy - Abstract
Objective. Dilatation of the intercellular space (DIS) of the esophageal epithelium is recognized as one of the earliest histological changes in gastroesophageal reflux disease patients. At the human gastroesophageal junction, reactive nitrogen oxide species (RNOS) are generated luminally through the entero-salivary re-circulation of dietary nitrate. In cases with gastroesophageal reflux, the site of luminal RNOS generation may shift to the distal esophagus. The aim of this study was to investigate whether luminal RNOS exposure could be involved in the pathogenesis of DIS. Material and methods. Rat esophageal mucosa was studied with an Ussing chamber model. On the luminal side of the chamber, RNOS were generated by the acidification of physiologic concentrations of sodium nitrite (1.0 or 5.0 mM). Esophageal barrier function was assessed by means of electrophysiological transmembrane resistance and membrane permeability by means of 3H-mannitol flux. The dimensions of the intercellular spaces were assessed by using transmission electron microscopy. Results. Administration of acid plus sodium nitrite induced DIS of the esophageal epithelium, and this ultrastructural morphological change was accompanied by a concomitant decrease in the transmembrane resistance and an increase in the epithelial permeability. The DIS induced by luminal RNOS was also confirmed in an in vivo exposure model. Conclusions. The present animal study indicates that the RNOS generated by the acidification of salivary nitrite in the presence of refluxed gastric acid in the esophagus could be a luminal factor that is responsible for the induction of DIS. Further studies are warranted to investigate the clinical relevance of the present findings to the human situation. [ABSTRACT FROM AUTHOR]
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- 2010
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10. Drosophila models of Alzheimer's amyloidosis: the challenge of dissecting the complex mechanisms of toxicity of amyloid-beta 42.
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Iijima K, Iijima-Ando K, Iijima, Koichi, and Iijima-Ando, Kanae
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Alzheimer's disease (AD) is the most common form of senile dementia, and a cure is desperately needed. The amyloid-beta42 (Abeta42) has been suggested to play a central role in the pathogenesis of AD. However, the mechanism by which Abeta42 causes AD remains unclear. To understand the pathogenesis and to develop therapeutic avenues, it is crucial to generate animal models of AD in genetically tractable organisms. Drosophila is a well-established model system for which abundant genetic tools are available. Moreover, its well organized brain permits the study of complex behaviors such as learning and memory. We have established transgenic flies that express human Abeta42 in the nervous system. These flies developed age-dependent short-term memory impairment and neurodegeneration. In this review, we will first describe transgenic Abeta42 fly models and discuss the unique features of this system compared to mouse AD models. Secondly, we will discuss the usage of the fly models to evaluate currently proposed therapeutic strategies. Thirdly, we will briefly review the results of a genetic screen for modifiers of Abeta42 toxicity in the fly model. Finally, we will discuss how to dissect the complex mechanisms of Abeta42 toxicity focusing on its aggregation propensity using the fly model system. [ABSTRACT FROM AUTHOR]
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- 2008
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11. Disruption of gastric barrier function by luminal nitrosative stress: a potential chemical insult to the human gastro-oesophageal junction.
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Ara, N., Iijima, K., Asanuma, K., Yoshitake, J., Ohara, S., Shimosegawa, T., and Yoshimura, T.
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GASTROESOPHAGEAL reflux , *NITRIC oxide , *RATS , *ANIMAL models in research , *DOUBLE-contrast examination , *MEDICAL research - Abstract
Objective: The human gastro-oesophageal junction is exposed to abundant amounts of luminal reactive nitrogen oxide species (RNOS) derived from the enterosalivary recirculation of dietary nitrate. The aim of this study is to investigate the direct effects of luminal RNOS on the adjacent gastric barrier function using an ex vivo chamber model. Methods: A chamber model in which the rat gastric mucosal membrane was mounted between the two halves of a chamber was designed to simulate the microenvironment of the lumen and the adjacent mucosa of the gastro-oesophageal junction. On the mucosal side of the chamber, RNOS were generated by the acidification of physiological concentrations of sodium nitrite. The epithelial barrier function was evaluated by electrophysiological transmembrane resistance, and membrane permeability with [³H]mannitol flux. The expression of occludin was evaluated by immunohistochemistry and immunoblotting. Dinitrosyl dithiolato iron complex (DNIC) was also measured by means of electron paramagnetic resonance spectroscopy to confirm the diffusion of RNOS from the mucosal lumen into the mounted mucosa. Results: The administration of acidified nitrite to the mucosal lumen caused both a decrease in transmembrane resistance and an increase in epithelial permeability, suggesting a disturbance of the gastric barrier function. These changes were accompanied by a derangement of the expression of occludin. The diffusion of luminal RNOS into the mounted membrane was confirmed by showing the generation of DNIC within the tissue. Conclusions: Simulating the microenvironment of the human gastro-oesophageal junction, this study demonstrated that RNOS generated luminally at the human gastro-oesophageal junction can derange the barrier function of the adjacent tissue by disrupting the tight junction. [ABSTRACT FROM AUTHOR]
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- 2008
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12. Homologous recombination repair is regulated by domains at the N- and C-terminus of NBS1 and is dissociated with ATM functions.
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Sakamoto, S., Iijima, K., Mochizuki, D., Nakamura, K., Teshigawara, K., Kobayashi, J., Matsuura, S., Tauchi, H., and Komatsu, K.
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PROTEINS , *ATAXIA , *TELANGIECTASIA , *T cells , *SISTER chromatid exchange , *GENETIC mutation - Abstract
The proteins responsible for radiation sensitive disorders, NBS1, kinase ataxia-telangiectasia-(A-T)-mutated (ATM) and MRE11, interact through the C-terminus of NBS1 in response to the generation of DNA double-strand breaks (DSBs) and are all implicated in checkpoint regulation and DSB repair, such as homologous recombination (HR). We measured the ability of several NBS1 mutant clones and A-T cells to regulate HR repair using the DR-GFP or SCneo systems. ATM deficiency did not reduce the HR repair frequency of an induced DSB, and it was confirmed by findings that HR frequencies are only slightly affected by deletion of ATM-binding site at the extreme C-terminus of NBS1. In contrast, The HR-regulating ability is dramatically reduced by deletion of the MRE11-binding domain at the C-terminus of NBS1 and markedly inhibited by mutations in the FHA/BRCT domains at the N-terminus. This impaired capability in HR is consistent with a failure to observe MRE11 foci formation. Furthermore, normal HR using sister chromatid was completely inhibited by the absence of FHA/BRCT domains. These results suggested that the N- and C-terminal domains of NBS1 are the major regulatory domains for HR pathways, very likely through the recruitment and retention of the MRE11 nuclease to DSB sites in an ATM-independent fashion.Oncogene (2007) 26, 6002–6009; doi:10.1038/sj.onc.1210428; published online 26 March 2007 [ABSTRACT FROM AUTHOR]
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- 2007
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13. Fe–S cluster proteins are intracellular targets for nitric oxide generated luminally at the gastro-oesophageal junction
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Asanuma, K., Iijima, K., Ara, N., Koike, T., Yoshitake, J., Ohara, S., Shimosegawa, T., and Yoshimura, T.
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NITRIC oxide , *PROTEINS , *MAGNETIC resonance , *CLINICAL pathology - Abstract
Abstract: In human, high concentrations of nitric oxide are generated at the gastro-oesophageal junction through entero-salivary recirculation of dietary nitrate. Nitric oxide is known to have a high affinity for Fe–S cluster proteins. The aim of this study is to investigate whether nitric oxide arising from the lumen diffuses into the adjacent tissue where it can interact with Fe–S proteins both in a rat animal model and human. An electron paramagnetic resonance detectable complex, dinitrosyl dithiolato iron complex (DNIC), was used as a biomarker for the interaction between Fe–S proteins and nitric oxide. The generation of the complex was evaluated in resected gastric tissue of nitrite-administered rat or biopsy specimens from human after nitrate ingestion. The activity of aconitase, one of the Fe–S cluster proteins, was also determined. The signal of the complex was observed at the rat gastro-oesophageal junction where luminal generation of nitric oxide from nitrite was maximal, and the intensity increased in a dose- and time-dependent manner. The appearance of the complex was accompanied by a significant inhibition of the aconitase activity at that site. The complex appeared in biopsy specimens from the gastro-oesophageal junction in three of five men after nitrate ingestion. Since DNIC is considered to be a decomposition product when Fe–S cluster proteins interact with nitric oxide, the appearance of the signal provides direct evidence that nitric oxide arising from the lumen can destroy such proteins. DNIC formation may represent the cellular mechanism responsible for the high prevalence of disease at the gastro-oesophageal junction. [Copyright &y& Elsevier]
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- 2007
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14. Lattice-free finite difference method for numerical solution of inverse heat conduction problem.
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Iijima, K. and Onishi, K.
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HEAT conduction , *TEMPERATURE , *BOUNDARY value problems , *DISTRIBUTION (Probability theory) , *EXPONENTIAL functions - Abstract
Inverse heat conduction problem consists of finding an initial temperature distribution from the knowledge of a distribution of the temperature at the present time. Here, we assume that the associated boundary conditions are known. The heat conduction problem backward in time is a typical example of ill-posed problems in the sense that the solution exists only for regular functions of some kind describing the present temperature distribution and also the solution is unstable for the present temperature distribution function. Conventional numerical methods often suffer from instability of the problem itself when high accuracy is intended in the approximation. Our aim is to create a meshless method which is applicable to the ill-posed inverse heat conduction problem. We construct a high order finite difference method in which quadrature points do not need to have a lattice structure. In order to develop our new method we show a tool in using exponential functions in Taylor's expansion. From numerical experiments we confirmed that our method is effective for solving two-dimensional inverse heat conduction problem numerically subject to mixed boundary conditions. [ABSTRACT FROM AUTHOR]
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- 2007
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15. Evaluation of imaging plate technique coupled with activation detector as the passive neutron monitor.
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Masumoto, K., Iijima, K., Toyoda, A., and Wang, Q.
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NEUTRONS , *ACTIVATION (Chemistry) , *RADIOACTIVITY , *DETECTORS , *ALUMINUM , *GOLD , *DIMENSIONAL analysis - Abstract
The spatial distribution of neutrons was measured at the muon science laboratory of KEK by the activation detector method using an imaging plate for the radioactivity measurement. It was confirmed that this method is highly sensitive to detect the average neutron dose of 10 µSv/h. The distribution of thermal and epithermal neutrons was also measured in the experimental room. The cadmium ratio inside the experimental room is one except for the neutron leakage point. The spatial distribution of neutrons inside the concrete shield of KENS was measured by the same method. Aluminum and gold foils were used for the measurement of fast and thermal neutrons, respectively. Two dimensional change of the reaction rate of the 27Al(n,α)24Na reaction shows a good agreement with the results calculated by the Monte Carlo simulation using MARS14 code. Thermal and epithermal neutron flux ratio on the beam axis was measured by the cadmium ratio method. The flux ratios were about 30 and almost constant for every slot except for the surface of the shield, because the cadmium ratio is 2. This method was very useful to measure the activity of many pieces of detector simultaneously without any efficiency and decay correction. Wide dynamic range and high sensitivity are also the merit of this method. [ABSTRACT FROM AUTHOR]
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- 2007
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16. horC confers beer-spoilage ability on hop-sensitive Lactobacillus brevis ABBC45cc.
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Iijima, K., Suzuki, K., Ozaki, K., and Yamashita, H.
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BEER spoilage , *LACTIC acid bacteria , *LACTOBACILLUS , *PLASMIDS , *MULTIDRUG resistance , *GENETIC markers , *BREWING , *CYTOPLASMIC inheritance - Abstract
Aims: To determine whether horC confers beer-spoilage ability and to evaluate the validity of horC as a trans-species genetic marker for differentiating the beer-spoilage ability of lactic acid bacteria (LAB). Methods and Results: Hop-sensitive Lactobacillus brevis ABBC45cc was transformed with an expression plasmid, pHYc horBC, containing putative multidrug resistance gene horC and its putative regulator horB, and the transformant was designated as ABBC45cc/pHYc horBC. As a control, ABBC45cc was transformed with pHYc horB that contains horB, and the transformed strain was designated as ABBC45cc/pHYc horB. As a result of beer-spoilage assay of these transformants, ABBC45cc/pHYc horBC exhibited beer-spoilage ability, whereas ABBC45cc/pHYc horB did not. Furthermore ABBC45cc/pHYc horBC showed higher hop resistance than ABBC45cc/pHYc horB, accounting for the differences in beer-spoilage ability observed between the two transformants. ABBC45cc/pHYc horBC also exhibited higher resistance to various structurally unrelated drugs, compared with ABBC45cc/pHYc horB. Conclusions: horC was shown to confer hop resistance and beer-spoilage ability on ABBC45cc by presumably encoding a multidrug transporter. Significance and Impact of the Study: The finding that horC plays an important role in hop resistance and beer-spoilage ability supports the validity of horC as a trans-species genetic marker for differentiating the beer-spoilage ability of LAB. [ABSTRACT FROM AUTHOR]
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- 2006
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17. High-dose mizoribine treatment for adolescents with systemic lupus erythematosus.
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Nozu K, Iijima K, Kamioka I, Fujita T, Yoshiya K, Tanaka R, Nakanishi K, Yoshikawa N, and Matsuo M
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- 2006
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18. Nitrate and nitrosative chemistry within Barrett's oesophagus during acid reflux.
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Suzuki, H., Iijima, K., Scobie, G., Fyfe, V., and McColl, K. E. L.
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ESOPHAGEAL cancer , *NITROSATION , *GASTRIC diseases , *VITAMIN C , *NITRIC oxide , *SALIVA - Abstract
Background and aims: When saliva, with its high nitrite content derived from the enterosalivary recirculation of dietary nitrate, meets acidic gastric juice, the nitrite is converted to nitrous acid, nitrosative species, and nitric oxide. In healthy volunteers this potentially mutagenic chemistry is focused at the gastric cardia. We have studied the location of this luminal chemistry in Barrett's patients during acid reflux. Methods: Ten Barrett's patients were studied before and after administration of 2 mmol nitrate. Using microdialysis probes we measured nitrite, ascorbic acid, total vitamin C, and thiocyanate concentrations and pH simultaneously in the proximal oesophagus, Barrett's segment, hiatal sac, proximal stomach, and distal stomach. In a subgroup, real time nitric oxide concentrations were also measured. Results: During acid reflux, Barrett's segment was the anatomical site with maximal potential for acid catalysed nitrosation, with its median concentration of nitrite exceeding that of ascorbic acid in two of 10 subjects before nitrate and in four of nine after nitrate. Thiocyanate, which catalyses acid nitrosation, was abundant at all anatomical sites. On entering the acidic Barrett's segment, there was a substantial fall in nitrite and the lowest ascorbic acid to total vitamin C ratio, indicative of reduction of salivary nitrite to nitric oxide at this anatomical site. Episodes of acid reflux were observed to generate nitric oxide concentrations of up to 60 μM within the Barrett's segment. Conclusion: The interaction between acidic gastric refluxate and nitrite rich saliva activates potentially mutagenic luminal nitrosative chemistry within Barrett's oesophagus. [ABSTRACT FROM AUTHOR]
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- 2005
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19. Diffusion of cytotoxic concentrations of nitric oxide generated luminally at the gastro-oesophageal junction of rats.
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Ascnuma, K., Iijima, K., Sugata, H., Ohara, S., Shimosegawa, T., and Yoshimura, T.
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ESOPHAGOGASTRIC junction , *NITRIC oxide , *LABORATORY rats , *NITROGEN compounds , *ESOPHAGUS , *GLUTATHIONE - Abstract
Background: In humans, high concentrations of nitric oxide are generated luminally at the gastro- oesophageal junction through enterosalivary recirculation of dietary nitrate. Aim: To investigate whether luminal nitric oxide can diffuse into the adjacent digestive tissue and alter tissue integrity. Methods: We designed an animal model using Wistar rats in which physiological concentrations of nitrite and acidified ascorbic acid were administered separately so that the two reactants first meet to form nitric oxide at the gastro-oesophageal junction. Luminal and tissue concentrations of nitric oxide were measured with an electrode and an electron paramagnetic resonance spectrometer, respectively. Concentrations of glutathione in the tissue were measured as a marker of nitrosative stress. n; Results: High concentrations of luminal nitric oxide were generated locally at the gastro-oesophageal junction of nitrite administered rats, reproducing a phenomenon observed in humans. High levels of nitric oxide were also detected largely in the superficial epithelium of the gastro-oesophageal junction. The concentration of I tissue glutathione at the gastro-oesophageal junction was significantly lower in nitrite administered rats compared with control rats, whereas that in the distal stomach was similar in the two rat groups. Conclusions: Using an animal model, this study demonstrated that nitric oxide generated in the lumen diffuses into the adjacent gastric tissue to a substantial degree, leading to localised consumption of glutathione in the tissue. Nitrosative stress induced by this mechanism may be involved in the high prevalence of inflammation and metaplasia, and subsequent development of neoplastic disease at this site. [ABSTRACT FROM AUTHOR]
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- 2005
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20. A practical method for torsional strength assessment of container ship structures
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Iijima, K., Shigemi, T., Miyake, R., and Kumano, A.
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CONTAINER ships , *CONTAINERIZATION , *STRUCTURAL design , *LOAD factor design - Abstract
Abstract: Container ship structures are characterized by large hatch openings. Due to this structural property, they are subject to large diagonal deformations of hatch openings and warping stresses under complex torsional moments in waves. This necessitates torsional strength assessment of hull girder of container ships in their structural design stage. In this paper, a practical method for torsional strength assessment of container ship structures with transparent and consistent background is discussed based on the results from up-to-date analyses. In order to estimate the torsional response characteristics as accurately as possible, three-dimensional Rankine source method, after being validated by tank tests, is employed for estimation of wave loads on a container ship, and FE analyses are conducted on the entire-ship model under the estimated loads. Then, a dominant regular wave condition under which the torsional response of the container ship becomes maximum is specified. Design loads for torsional strength assessment that give torsional response equivalent to the long-term predicted values of torsional response are investigated based on the torsional moments on several container ships under the specified dominant wave condition. An appropriate combination of stress components to estimate the total hull girder stress is also discussed. [Copyright &y& Elsevier]
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- 2004
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21. Gastric Acid Secretion of Normal Japanese Subjects in Relation to Helicobacter pylori Infection, Aging, and Gender.
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Iijima, K., Ohara, S., Koike, T., Sekine, H., and Shimosegawa, T.
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HELICOBACTER pylori infections , *GASTRIC acid , *AGE factors in disease , *SEX factors in disease , *SECRETION - Abstract
Background: In Japan. where the incidence of gastric cancer is high. Helicobacter pylori infection could affect gastric acid secretion differently from that in Western countries. The aim of this study was to investigate the relationship between H. pylori infection, acid secretion, aging, and gender in normal Japanese subjects. Methods: The study comprised 193 Japanese subjects who had undergone routine endoscopy. Gastrin-simulated acid output was performed during the routine endoscopic examination using the endoscopic method of gastric acid secretory testing (EGT: endoscopic gastrin test), which has been reported previously. H. pylori status was determined by histology, rapid urease test, and serology. Results: Mean EGT values were 3.9 ± 1.5 mEq/10 min in H. pylori-negative men, 1.6 ± 2.5 in H. pylori-positive men, 2.2 ± 0.9 in H. pylori-negative women, and 1.5 ± 1.2 in H. pylori-positive women. Although acid secretion was lower in H. pylori-positive subjects compared with H. pylori-negative subjects in both men and women, the decrease was more marked in men with H. pylori infection. Multiple linear regression analysis showed that aging is positively associated with gastric acid secretion in the H. pylori-negative subjects, whereas a negative association was found between them in the H. pylori-positive subjects. Conclusions: In Japanese subjects, aging affects gastric acid secretion differently depending on the status of H. pylori infection. H. pylori infection showed a stronger inhibitory effect on the acid secretion in men than in women. This gender-related difference in the susceptibility acid secretion to H. pylori infection may explain the higher rates of gastric cancer in men in Japan. [ABSTRACT FROM AUTHOR]
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- 2004
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22. Long-term effect of.
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Iijima, K., Sekine, H., Koike, T., Imatani, A., Ohara, S., and Shimosegawa, T.
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ACHLORHYDRIA , *HELICOBACTER pylori infections , *HELICOBACTER pylori , *THERAPEUTICS , *GASTRIC acid , *GASTRITIS - Abstract
: Although profound hypochlorhydria is considered to be an important risk factor for development of gastric cancer, long-term effect of Helicobacter pylori eradication on its reversibility remains uncertain. : To clarify the change in acid secretion after eradication in a long-term follow-up over 5 years in patients with profound hypochlorhydria. : Twenty-three H. pylori-positive patients with hypochlorhydria (<0.6 mmol/10 min) were enrolled prospectively. Assessment of gastrin-stimulated acid output and histologic evaluation of biopsy specimens were performed prior to, and 1, 7 months after eradication. Subsequently, gastric acid secretion was assessed for long-term period over 5 years after eradication in 12 patients. : Gastric acid secretion was reversed to normal range in nine of 23 patients (39%) at 7 months after eradication. In the long-term follow-up, gradual and significant recovery in gastric acid secretion was observed up to 2 years post-therapy. However, there was no additional increase during the last 3 years of 5-year follow-up period, leaving the acid secretory levels subnormal in the majority of the patients. : This long-term follow-up study suggests that the pathologic process has already progressed to an irreversible stage in the majority of H. pylori-positive patients with marked body atrophy and profound hypochlorhydria. [ABSTRACT FROM AUTHOR]
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- 2004
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23. Conditions for acid catalysed luminal nitrosation are maximal at the gastric cardia.
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Suzuki, H., Iijima, K., Moriya, A., McElroy, K., Scobie, G., Fyfe, V., and McColl, K.E.L.
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NITRITES , *GASTRIC acid - Abstract
Background: Saliva has a high nitrite concentration, derived from the enterosalivary recirculation of dietary nitrate, and is the main source of nitrite entering the acidic stomach. Acidification of nitrite in the presence of secondary amines or amides generates potentially carcinogenic N-nitroso compounds. The reaction is inhibited by ascorbic acid and catalysed by thiocyanate. Aim: To determine whether there is intragastric regional variation in the chemical conditions promoting luminal nitrosation following nitrate ingestion. Methods: Using microdialysis probes, we measured concentrations of nitrite, ascorbic acid, total vitamin C, and thiocyanate simultaneously in saliva, the distal oesophagus, cardia, and the proximal and distal stomach of 17 healthy volunteers before and following intragastric nitrate (2 mmol) administration. Results: The median pH in the distal oesophagus, cordia, and proximal and distal stomach were 7, 2.6, 1.9, and 1.7, respectively, before, and were similar following nitrate administration. Mean nitrite concentration in the distal oesophagus was similar to that of saliva, being 29.1 µM and 36.7 µM, respectively, before nitrate and increasing to 181.6 µM and 203.3 µM after nitrate ingestion. Within the stomach, mean (SEM) nitrite concentration following nitrate was higher in the cordia (45.5 (12.7) µM) than in the mid (7.8 (3.1)) (p<0.01) or distal (0.8 (0.6)) (p<0.1) stomach, and ascorbic acid concentration was lower at the cordia (13.0 (6.1)) than in the mid (51 (19.2)) (p<0.02) or distal (86 (29)) (p<0.01) stomach. Consequently, the median ascorbic acid to nitrite ratio was lowest at the cardia (0.3) (p<0.01) versus the mid (7.8) or distal (40) stomach. Thiocyanate concentration was similar throughout the stomach. Conclusions: The conditions favouring luminal generation of N-nitroso compounds from dietary nitrate are maximal at the most proximal cordia region of the acidic stomach and may contribute to the high incidence of mutagenesis at this site. [ABSTRACT FROM AUTHOR]
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- 2003
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24. Recovery from cyclosporine-associated arteriolopathy in childhood nephrotic syndrome.
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Hamahira, Kiyoshi, Iijima, K., Tanaka, Ryojiro, Nakamura, Hajime, and Yoshikawa, Norishige
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NEPHROTIC syndrome in children , *CYCLOSPORINE , *RENAL biopsy , *DRUG efficacy - Abstract
Cyclosporine (CS) is well recognized to be effective in the treatment of children with steroid-dependent and steroid-resistant nephrotic syndrome (NS), but its use can result in chronic nephrotoxicity. The histological changes that occur after CS discontinuation are unknown. Therefore, we examined the histological changes [CS-associated arteriolopathy (CAA), tubulointerstitial lesions, and focal glomerular lesions] in renal biopsy specimens after the drug had been discontinued in eight children with idiopathic nephrotic syndrome (NS). These children had been treated with long-term moderate-dose CS and had shown mild-to-moderate chronic CS nephrotoxicity. The degree of CAA improved significantly after CS discontinuation (mean CAA grade from 1.30±0.46 to 0.25±0.46, P=0.028). CAA disappeared in six of these children after CS discontinuation. However, the tubulointerstitial lesions and the focal glomerular lesions did not change after CS discontinuation. In conclusion, in children with idiopathic NS, CAA is improved by discontinuation of CS, but tubulointerstitial changes and focal glomerular lesions do not regress with drug discontinuation. [ABSTRACT FROM AUTHOR]
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- 2001
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25. Study of Overwritten Magnetization at the Off-Track Position.
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Nomura, A., Iijima, K., Haseba, Y., and Shiiki, K.
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MAGNETIC recorders & recording , *MAGNETIC recording heads - Abstract
Presents a study that investigated overwritten magnetization at the off-track position using micro-magnetic simulation employing the Landau-Lifshitz-Gilbert equation. Background on the influence of the head position on recording efficiency; Methodology; Results and discussion.
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- 2001
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26. Expression of thrombopoietin receptor and its functional role in human B-precursor leukemia cells with 11q23 translocation or Philadelphia chromosome.
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Iijima, K, Sugita, K, Inukai, T, Goi, K, Tezuka, T, Uno, K, Sato, H, Kagami, K, and Nakazawa, S
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THROMBOPOIETIN , *ACUTE leukemia - Abstract
Thrombopoietin (TPO) is a hematopoietic growth factor which plays a central role in normal megakaryocytopoiesis and thrombopoiesis. Although the interaction between TPO and its receptor c-Mpl encoded by the c-mpl gene is now known to be implicated in the proliferation and/or differentiation of abnormal myeloid cells and normal hematopoietic stem cells, little is known about a role of the TPO/c-Mpl system in lymphoid leukemia cells. In the present study, we first examined the expression of c-mpl/c-Mpl in 23 human lymphoid leukemic cell lines (T-lineage 4, B-lineage 19) using three distinct methods. The c-mpl mRNA was detectable in as many as 20 cell lines (T-lineage 3, B-lineage 17) by reverse transcriptase-polymerase chain reaction, but its translated product, c-Mpl, was demonstrable by Western blot only in B-lineage cell lines. Flow cytometric analysis revealed the surface c-Mpl expression in 13 of 17 B-lineage cell lines, but its higher expression (>40%) was restricted in nine B-precursor cell lines, eight of which had 11q23 translocation or Philadelphia chromosome (Ph1). We also demonstrated that two of eight cell lines with 11q23 translocation or Ph1 exhibited a significant proliferative response to TPO in the 3H-thymidine uptake and colony-forming assays. Triggering of these cell lines by TPO transiently up-regulated tyrosine phosphorylation of JAK-2 and Shc, indicating that their receptor is functional. Primary leukemia cells separated from patients with B-precursor acute lymphoblastic leukemia with Ph1 or 11q23 translocation also showed the surface c-Mpl expression and a significant responsiveness to TPO. These results suggest that the TPO/c-Mpl interaction may play a physiological role in the growth regulation of B-precursor leukemia cells particularly with specific chromosomal abnormalities. [ABSTRACT FROM AUTHOR]
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- 2000
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27. Preparation of ferroelectric BaTiO3 thin films by activated reactive evaporation.
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Iijima, K., Terashima, T., Yamamoto, K., Hirata, K., and Bando, Y.
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FERROELECTRIC thin films , *BARIUM compounds , *STRONTIUM compounds , *PLATINUM - Abstract
Ferroelectric BaTiO3 thin films were directly and epitaxially grown on SrTiO3 single crystal and epitaxial Pt film substrates by activated reactive evaporation. The substrate temperature was around 600 °C. For (100) oriented as-grown films, a typical ferroelectric hysteresis loop and a maximum of dielectric constant at about 115 °C were observed. The resistivity was as high as 109 Ω cm and the breakdown voltage was 2.7 MV/cm for as-grown BaTiO3 films. [ABSTRACT FROM AUTHOR]
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- 1990
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28. Erratum: Epitaxial growth and dielectric properties of BaTiO3 films on Pt electrodes by reactive evaporation [J. Appl. Phys. 76, 7833 (1994)].
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Yano, Y., Iijima, K., Daitoh, Y., Terashima, T., Bando, Y., Watanabe, Y., Kasatani, H., and Terauchi, H.
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EPITAXY , *DIELECTRICS - Abstract
Presents corrections for the study 'Epitaxial Growth and Dielectric Properties of BaTiO[sub3] Films on Pt Electrodes by Reactive Evaporation,' by Y. Kano, K. Ijima, T. Terashima, Y. Bando, Y. Watanabe, H. Kasatani and H. Terauchi.
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- 1995
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29. NOVEL MECHANISM OF NITROSATIVE STRESS FROM DIETARY NITRATE RELEVANT TO GASTROESOPHAGEAL JUNCTION CANCER.
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Iijima, K., Grant, J., McElroy, K., Anderson, S., Fyfe, V., Paterson, S., Preston, T., and McColl, K.E.L.
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NITRIC oxide , *ESOPHAGOGASTRIC junction , *GASTRIC juice - Abstract
High concentrations of nitric oxide are generated at the gastro-oesophageal (GO) junction due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice containing ascorbic acid. Salivary nitrite is derived from the enterosalivary recirculation of dietary nitrate. Aims: To determine whether nitric oxide generated in the above way will exert nitrosative stress on the adjacent epithelium. Methods: A benchtop model was constructed reproducing the chemistry occurring at the GO junction and incorporating an epithelial compartment maintained at pH 7.4 separated from the lumen by a thin hydrophobic barrier. The secondary amine morpholine was added to each compartment and N-nitrosomorpholine formation at 15 min measured. Results: Adding 100µM nitrite to the acidic (pH 1.5) luminal compartment in the absence of ascorbic acid generated 6.2±2.0 (mean±SE) N-nitrosomorpholine in that compartment and 2.2±0.1 µM in the epithelial compartment. When 100µM nitrite was added to the acidic luminal compartment (pH 1.5) containing ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused into the adjacent epithelial compartment (pH 7.4) where it generated very high concentrations of N-nitrosomorpholine (137±5.6µM). The addition of ascorbic acid or glutathione to the epithelial compartment only reduced this nitric oxide induced nitrosation within the epithelial compartment by 40%. Conclusion: Ascorbic acid in gastric juice prevents acid-catalysed nitrosation within the gastric lumen. However, in doing so it generates nitric oxide which exerts a far higher nitrosative stress on the adjacent epithelium. This mechanism may be relevant to the aetiology of mutagenesis at the GO junction. [ABSTRACT FROM AUTHOR]
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- 2003
30. IN BARRETT'S OESOPHAGUS, ACID REFLUX GENERATES HIGH CONCENTRATIONS OF NITRIC OXIDE DERIVED FROM DIETARY NITRATE.
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Suzuki, H., Iijima, K., Henry, E., McElroy, K., Scobie, G., and McColl, K.E.L.
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ESOPHAGUS , *NITRATES , *MUTAGENESIS - Abstract
Background: The lumen of the oesophagus has a high nitrite concentration due to the enterosalivary recirculation of dietary nitrate. On entering the acidic stomach, the nitrite is converted to nitric oxide, which may contribute to mutagenesis at the cardia. Aim: To study luminal nitrite chemistry in patients with Barrett's oesophagus. Methods: Using microdialysis probes, we studied nitrite concentration in saliva, proximal oesophagus within the Barrett's segment, and proximal and distal stomach of 10 Barrett's patients before and following nitrate (2 mmol) administration. Results were compared with 17 healthy controls. In a subgroup of Barrett's patients, we simultaneously monitored oesophageal pH and nitric oxide concentration. Results: In the healthy controls, a high nitrite concentration was present in saliva (mean fasting = 37 µM, after nitrate = 203 µM) and throughout the length of the oesophagus (fasting = 29 µM, after nitrite = 181 µM) but fell by 75% on entering the acidic gastric cardia. The fall in nitrite was associated with a high cardia concentration of nitric oxide (fasting = 2.4 µM, after nitrite = 7.5 µM). In the Barrett's patients, similarly high concentrations of nitrite were present in saliva and in the proximal oesophagus but the nitrite concentration fell by 98% on entering the Barrett's segment exposed to acid reflux. Simultaneous recording of pH and nitric oxide concentration within the Barrett's segment indicated that the reflux of acidic gastric juice into the Barrett's segment resulted in the immediate generation of high concentrations of nitric oxide within the oesophageal lumen (fasting = 13 µM, after nitrate = 20 µM). Conclusions: The lumen of the normal oesophagus contains high concentrations of nitrite derived from the enterosalivary recirculation of dietary nitrate. The reflux of acidic gastric juice into the distal oesophagus immediately converts the nitrite to nitric oxide. The... [ABSTRACT FROM AUTHOR]
- Published
- 2003
31. BISPHOSPHONATES INHIBIT VASCULAR CALCIFICATION VIA TWO DISTINCT UNIQUE PROPERTIES, INHIBITION OF PHOSPHATE COTRANSPORT AND RESTORATION OF CELL SURVIVAL PATHWAY
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Iijima, K., Son, B., Ito, Y., Mochizuki, S., Yamada, Y., Takemura, A., Fukai, S., Nomura, K., Ota, H., Ogawa, S., Eto, M., Akishita, M., and Ouchi, Y.
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- 2008
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32. 3P-0692 MHG-CoA reductase inhibitors inhibit human vascular smooth muscle cell calcification — Another pleiotropic effect of statins
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Son, B., Iijima, K., Kozaki, K., Watanabe, T., Ohike, Y., Kojima, T., Yu, J., Miyahara, Y., and Ouchi, Y.
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- 2003
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33. IL-33 mediates reactive eosinophilopoiesis in response to airborne allergen exposure.
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Anderson, E. L., Kobayashi, T., Iijima, K., Bartemes, K. R., Chen, C.‐C., and Kita, H.
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INTERLEUKIN-33 , *EOSINOPHIL disorders , *ALLERGENS , *AIRBORNE infection , *BONE marrow diseases , *LABORATORY mice - Abstract
Background Exposure to aeroallergens induces eosinophilic airway inflammation in patients with asthma and allergic airway diseases. The circulating number of eosinophils in peripheral blood is relatively small, leading us to hypothesize that bone marrow needs to be engaged quickly to meet the demands of the tissues. Methods To investigate the communication between the lungs and bone marrow, we used acute allergen exposure and airway inflammation models in mice. Gene-deficient mice and cytokine reporter mice as well as in vitro cell culture models were used to dissect the mechanisms. Results Naïve BALB/c mice produced increased numbers of eosinophil precursors and mature eosinophils in the bone marrow when their airways were exposed to a common fungal allergen, Alternaria alternata. Expression of IL-5 and IL-33 increased rapidly in the lungs, but not in the bone marrow. Sera from allergen-exposed mice promoted eosinophilopoiesis in bone marrow cells from naïve mice, which was blocked by anti- IL-5 antibody. Mice deficient in the IL-33 receptor ST2 (i.e., Il1rl1−/− mice) were unable to increase their serum levels of IL-5 and allergen-induced eosinophilopoiesis in the bone marrow after allergen exposure. Finally, group 2 innate lymphoid cells ( ILC2s) in the lungs showed robust expression of IL-5 after Alternaria exposure. Conclusions These finding suggests that lung IL-33, through innate activation of ILC2s and their production of IL-5, plays a key role in promoting acute reactive eosinophilopoiesis in the bone marrow when naïve animals are exposed to airborne allergens. Therefore, bone marrow eosinophilopoiesis may be affected by atmospheric environmental conditions. [ABSTRACT FROM AUTHOR]
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- 2016
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34. HLA-DR polymorphism modulates response to house dust mites in a transgenic mouse model of airway inflammation.
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Rajagopalan, G., Tilahun, A. Y., Iijima, K., David, C. S., Kita, H., and Juhn, Y. J.
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HLA histocompatibility antigens , *GENETIC polymorphisms , *HOUSE dust mites , *TRANSGENIC mice , *LABORATORY mice , *INFLAMMATION , *ASTHMA in children , *CYTOKINES - Abstract
We and others have reported that HLA-DRB1*03 is associated with childhood asthma. To extend this observation and to prove this association, we sensitized and challenged either HLA-DR2 (HLA-DRB1*1502) or HLA-DR3 (HLA-DRB1*0301) transgenic mice with house-dust mite extract. Inflammatory cell counts and cytokine levels in the bronchoalveolar lavage (BAL) fluid between HLA-DR3 and DR2 mice were compared. HLA-DR3 transgenic mice had significantly elevated eosinophil counts, Interleukin-4 and Interleukin-13 levels in the BAL fluid but not interferron gamma-γ. Thus, our study suggests that HLA-DRB1*0301 plays an important role in mounting a Th2-predominant immune response to house dust mite and Th2-type inflammation in the lung. [ABSTRACT FROM AUTHOR]
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- 2011
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35. Phase I study of Paclitaxel, Cisplatin and 5-fluorouracil combination chemotherapy for unresectable / recurrent gastric cancer.
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Kato, J., Nagahara, A., Iijima, K., Kodani, T., Higashihara, Y., Yoshimura, M., Serizawa, N., Osada, T., Yoshizawa, T., Otaka, M., and Watanabe, S.
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PACLITAXEL , *CISPLATIN , *FLUOROURACIL , *DRUG therapy , *STOMACH cancer - Abstract
Purpose: We investigated the safety of triple combination therapy by addition of Paclitaxel (PTX) to Cisplatin (CDDP) and 5-fluorouracil (5-FU) combination therapy, which was considered the conventional standard therapy for patients with unresectable / recurrent gastric cancer.Material and Methods: The doses of PTX and CDDP were fixed at 80 and 50 mg/m2. They were administered on days 1 and 8, followed by a resting period of 20 days. 5-FU 300 mg/m2 at a maximum dose of 500 mg/m2 was administered at levels 0 and 2, respectively, and the dose was increased by 100 mg/m2 until the maximum tolerated dose (MTD). It was administered on days 1 - 5 and 8 - 12, followed by a resting period of 16 daysResults: Twelve patients enrolled in this study. Of them, three patients were excluded from evaluation because treatment continuation was not feasible. There were 4 leukopenia and 7 neutropenia cases with hematological toxicity at grade 3 or higher. They were observed at all dose levels, but no case showed infection. In terms of non-hematological toxicity at grade 3 or higher, there were two patients with nausea and vomiting and two patients with diarrhea, one patient with mucositis, one patient with anorexia. All patients with non-hematological toxicity at grade 3 or higher were at level 2. The dose-limiting toxicity (DLT) was observed at level 2, and 5-FU at 400 mg (level 1) was adopted.Conclusions: We proved in this study that PTX, CDDP, and 5-FU combination chemotherapy was a safe treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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36. Radium uptake during barite recrystallization at 23±2°C as a function of solution composition: An experimental 133Ba and 226Ra tracer study
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Curti, E., Fujiwara, K., Iijima, K., Tits, J., Cuesta, C., Kitamura, A., Glaus, M.A., and Müller, W.
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RADIUM , *BARITE , *RECRYSTALLIZATION (Geology) , *POWDERS , *SOLUTION (Chemistry) , *ATMOSPHERIC pressure , *RADIOACTIVE tracers , *NUCLEAR activation analysis , *RADIOACTIVITY - Abstract
Abstract: High-purity synthetic barite powder was added to pure water or aqueous solutions of soluble salts (BaCl2, Na2SO4, NaCl and NaHCO3) at 23±2°C and atmospheric pressure. After a short pre-equilibration time (4h) the suspensions were spiked either with 133Ba or 226Ra and reacted under constant agitation during 120–406days. The pH values ranged from 4 to 8 and solid to liquid (S/L) ratios varied from 0.01 to 5g/l. The uptake of the radiotracers by barite was monitored through repeated sampling of the aqueous solutions and radiometric analysis. For both 133Ba and 226Ra, our data consistently showed a continuous, slow decrease of radioactivity in the aqueous phase. Mass balance calculations indicated that the removal of 133Ba activity from aqueous solution cannot be explained by surface adsorption only, as it largely exceeded the 100% monolayer coverage limit. This result was a strong argument in favor of recrystallization (driven by a dissolution–precipitation mechanism) as the main uptake mechanism. Because complete isotopic equilibration between aqueous solution and barite was approached or even reached in some experiments, we concluded that during the reaction all or substantial fractions of the initial solid had been replaced by newly formed barite. The 133Ba data could be successfully fitted assuming constant recrystallization rates and homogeneous distribution of the tracer into the newly formed barite. An alternative model based on partial equilibrium of 133Ba with the mineral surface (without internal isotopic equilibration of the solid) could not reproduce the measured activity data, unless multistage recrystallization kinetics was assumed. Calculated recrystallization rates in the salt solutions ranged from 2.8×10−11 to 1.9×10−10 molm−2 s−1 (2.4–16μmolm−2 d−1), with no specific trend related to solution composition. For the suspensions prepared in pure water, significantly higher rates (∼5.7×10−10 molm−2 s−1 or ∼49μmolm−2 d−1) were determined. Radium uptake by barite was determined by monitoring the decrease of 226Ra activity in the aqueous solution with alpha spectrometry, after filtration of the suspensions and sintering. The evaluation of the Ra uptake experiments, in conjunction with the recrystallization data, consistently indicated formation of non-ideal solid solutions, with moderately high Margules parameters (W AB =3720–6200J/mol, a 0 =1.5–2.5). These parameters are significantly larger than an estimated value from the literature (W AB =1240J/mol, a 0 =0.5). In conclusion, our results confirm that radium forms solid solutions with barite at fast kinetic rates and in complete thermodynamic equilibrium with the aqueous solutions. Moreover, this study provides quantitative thermodynamic data that can be used for the calculation of radium concentration limits in environmentally relevant systems, such as radioactive waste repositories and uranium mill tailings. [Copyright &y& Elsevier]
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- 2010
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37. Development of detection medium for hard-to-culture beer-spoilage lactic acid bacteria.
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Suzuki, K., Asano, S., Iijima, K., Kuriyama, H., and Kitagawa, Y.
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LACTIC acid bacteria , *MICROBIOLOGY , *MICROORGANISMS , *ANTIBACTERIAL agents , *LACTOBACILLUS , *FUNGUS-bacterium relationships - Abstract
Aims: To develop a detection medium for hard-to-culture beer-spoilage lactic acid bacteria (LAB). Methods and Results: Four hard-to-culture beer-spoilage strains of LAB, belonging to Lactobacillus paracollinoides and Lactobacillus lindneri, have been obtained by repeatedly subculturing the wild-type strains in beer. To develop a countermeasure against these hard-to-culture beer-spoilage LAB, a beer-based medium was modified. As a consequence, the supplementation of a small amount of de Man Rogosa Sharpe medium was found to enhance the growth of hard-to-culture beer-spoilage LAB strains obtained in this study. In addition, sodium acetate was shown to improve the selectivity of this beer-based medium. Further comparative study was performed with five other media widely used for the detection of beer-spoilage LAB in the brewing industry. This study revealed that the newly developed medium, designated advanced beer-spoiler detection (ABD) medium, possessed superior sensitivity for hard-to-culture beer-spoilage LAB and comparable sensitivity with easy-to-culture beer-spoilage LAB. Moreover, ABD medium was found to suppress the growth of nonspoilage micro-organisms, and thereby allow the selective growth of beer-spoilage LAB. Conclusions: Advanced beer-spoiler detection medium is considered as an effective tool for comprehensive detection of beer-spoilage LAB in breweries. Significance and Impact of the Study: The detection by ABD medium can be used as an indicator for differentiating the beer-spoilage ability of LAB without further confirmatory tests in breweries. [ABSTRACT FROM AUTHOR]
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- 2008
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38. Spatial changes in the distributions of deep-sea “Cerviniidae” (Harpacticoida, Copepoda) and their associations with environmental factors in the bathyal zone around Sagami Bay, Japan.
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Shimanaga, M., Nomaki, H., and Iijima, K.
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CERVINIIDAE , *HARPACTICOIDA , *AQUATIC animals , *MARINE animals , *SPECIES diversity , *BENTHOS , *AQUATIC biology - Abstract
To estimate species turnover rates on scales of several tens of km in deep-sea benthic animals, we analyzed spatial and inter-annual changes in species diversity and composition of cerviniids, a typical group of deep-sea harpacticoids, at stations in and around Sagami Bay, central Japan. Associations with environmental factors were also investigated. Generally, bathymetrical patterns in diversity of benthos are unimodal and peak at depths of 2,000–3,000 m. In Sagami Bay, cerviniid diversity did not follow this trend; both species richness and evenness were negatively correlated with water depth. Multivariate analyses [detrended correspondence analysis (DCA) and non-metric multi-dimensional scaling] suggested that temporal changes in species composition of cerviniids are smaller than spatial changes that occur on horizontal scales of several tens of km. Community structure does not change completely on these scales in the bathyal zone around Sagami Bay. DCA also showed that bathymetrical changes in species composition can be regulated by certain factors associated with water depth. [ABSTRACT FROM AUTHOR]
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- 2008
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39. Characterization of horA and its flanking regions of Pediococcus damnosus ABBC478 and development of more specific and sensitive horA PCR method.
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Suzuki, K., Sami, M., Iijima, K., Ozaki, K., and Yamashita, H.
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BACTERIA , *PLASMIDS , *LACTOBACILLUS , *POLYMERASE chain reaction , *MICROBIOLOGY - Abstract
Aims: To characterize horA and its flanking regions of Pediococcus damnosus ABBC478 and, on the basis of this insight, to develop a more specific and sensitive horA PCR method. Methods and Results: A plasmid harbouring the homologue of a hop-resistance gene, horA, was sequenced and designated pRH478. The nucleotide sequence and open reading frame structure of horA and its flanking regions of pRH478 were found to be highly similar to those of pRH45, a horA-harbouring plasmid previously identified in Lactobacillus brevis ABBC45. The nucleotide sequence of the horA homologue of P. damnosus ABBC478 was 99·6% identical with that of horA. Based on this insight, new primers specific to horA were designed and compared with the previously reported specific primer pair. As a consequence, it was demonstrated that the new primer pair is superior in specificity and sensitivity. Conclusions: The newly developed horA PCR method allows more specific and sensitive determination of the beer-spoilage ability of lactic acid bacteria (LAB). Significance and Impact of the Study: The nucleotide sequences of the horA homologues were found to be essentially identical among distinct species of LAB, indicating that horA-specific primers can be designed from almost any region of the horA gene. [ABSTRACT FROM AUTHOR]
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- 2006
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40. Activation energies of the self-diffusion of HTO, 22Na+ and 36Cl− in a highly compacted argillaceous rock (Opalinus Clay)
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Van Loon, L.R., Müller, W., and Iijima, K.
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WATER , *SOLUTION (Chemistry) , *SOLID solutions , *DIFFUSION - Abstract
Abstract: The temperature dependence of the self-diffusion of HTO, 22Na+ and 36Cl− in Opalinus Clay (OPA) was studied using a through-diffusion technique, in which the temperature was gradually increased in the steady state phase of the diffusion. The measurements were done on samples from two different geological locations. The dependence of the effective diffusion coefficient on temperature was found to be of an Arrhenius type in the temperature range between 0 and 70 °C. A slight difference between the two locations could be observed. The average value of the activation energy of the self-diffusion of HTO in OPA was 21.1±1.6 kJmol−1, and 21.0±3.5 and 19.4±1.5 kJmol−1 for 22Na+ and 36Cl−, respectively. The measured values for HTO are slightly higher than the values found for the bulk liquid water (HTO: 18.8±0.4 kJmol−1). This indicates that the structure of the confined water in OPA might be slightly different from that of bulk liquid water. Also for Na+ and Cl−, slightly higher values than in bulk liquid water (Na+: 18.4 kJmol−1; Cl−: 17.4 kJmol−1) were observed. The Stokes–Einstein relationship, based on the temperature dependency of the viscosity of bulk water, could not be used to describe the temperature dependence of the diffusion of HTO in OPA. This additionally indicates the slightly different structure of the pore water in OPA. [Copyright &y& Elsevier]
- Published
- 2005
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- View/download PDF
41. Validation of Microdialysis Probes for Studying Nitrosative Chemistry Within Localized Regions of the Human Upper Gastrointestinal Tract.
- Author
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Suzuki, H., Moriya, A., Iijima, K., McElroy, K., Fyfe, V.E., and McColl, K.E.L.
- Subjects
- *
DIALYSIS (Chemistry) , *NITROSATION , *GASTROINTESTINAL system - Abstract
Background: We have examined the suitability of microdialysis probes for examining nitrosative chemistry within localized regions of the lumen of the gastrointestinal tract. Chemical nitrosation occurs maximally at pH 2.5 in the presence of nitrite and thiocyanate and absence of ascorbic acid. Nitrite and thiocyanate are delivered into the stomach in saliva and ascorbic acid is secreted in gastric juice. Methods: We used a benchtop model to reproduce the nitrosative chemistry occurring in the human upper GI tract and assessed the ability of the microdialysis probes to measure it. Results: The microdialysis probes were reliable at measuring nitrite ascorbic acid, total vitamin C and thiocyanate in both aqueous solutions and human gastric juice over the full range of intragastric pH, i.e. 1.5, 2.5, 3.5, 5.0 and 7.0. The probes were also reliable at measuring these chemicals under conditions simulating the active interaction between nitrite and ascorbic acid. Under such conditions with ascorbic acid in excess the probes gave a more accurate assessment of the nitrite level than that obtained by directly sampling the gastric juice. This was due to the probes not being subject to artefactual measurement of nitric oxide as nitrite. This was prevented by the rapid diffusion of nitric oxide through the probe collecting tube. Conclusion: Microdialysis probes provide a reliable means of examining nitrosative chemistry within the lumen of the upper GI tract. In addition, they have the advantage of measuring this chemistry in very local regions and of simultaneously comparing the chemistry in different regions of the upper GI tract. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
42. Clinical significance of nm23-H1 proteins expressed on cell surface in non-Hodgkin’s lymphoma.
- Author
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Niitsu, N, Honma, Y, Iijima, K, Takagi, T, Higashihara, M, Sawada, U, and Okabe-Kado, J
- Subjects
- *
LYMPHOMAS , *PROTEINS - Abstract
The nm23 gene was isolated as a metastasis suppressor gene that exhibits low expression in high-level metastatic cancer cells. Its gene is related to the prognosis of acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL). In this study, we examined the expression of nm23-H1 protein on the lymphoma cell surface of NHL. In 28 of 108 cases (25.9%), we observed ≥20% of cell surface nm23-H1 protein expression and expression was especially high in peripheral T cell lymphomas and extranodal NK/T cell lymphomas. We also observed a significant correlation between serum nm23-H1 level and cell surface nm23-H1 expression levels. In patients with high levels of cell surface nm23-H1 expression, overall and progression-free survival rates were significantly lower than those in patients with low surface nm23-H1 expression levels. When surface nm23-H1 and serum nm23-H1 were combined, patients with high levels of both exhibited a poorer prognosis than patients with a high level of one or the other. These results indicate that in addition to serum nm23-H1, cell surface nm23-H1 may be used as a prognostic factor in planning a treatment strategy. The nm23-H1 protein appears to be intimately related to biological aggressiveness of lymphoma and, therefore, might be a molecular target of NHL treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
43. Apoptosis-inducing protein, AIP, from parasite-infected fish induces apoptosis in mammalian cells by two different molecular mechanisms.
- Author
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Murakawa, M, Jung, S-K, Iijima, K, and Yonehara, S
- Subjects
- *
PROTEINS , *APOPTOSIS , *CHUB mackerel , *ANISAKIS - Abstract
AlP (apoptosis-inducing protein) is a protein purified and cloned from Chub mackerel infected with the larval nematode, Anisakis simplex, which induces apoptosis in various mammalian cells including human tumor cell lines. AlP has shown structural and functional homology to Lamino acid oxidase (LAO) which oxidizes several L-amino acids including L-lysine and AlP-induced apoptosis has been suggested to be mediated by H[sub 2]O[sub 2] generated by LAO activity of AlP. In this study, we confirmed that recombinant AlP generated enough H[sub 2]O[sub 2] in culture medium to induce rapid apoptosis in cells and this apoptosis was clearly inhibited by co-cultivation with antioxidants such as catalase and Nacetyl-cysteine. Surprisingly, however, we found that AlP still could induce H[sub 2]O[sub 2]-independent apoptosis more slowly than H[sub 2]O[sub 2]-dependent one in HL-60 cells even in the presence of antioxidants. In addition, the HL-60-derived cell line HP100-1, which is a H[sub 2]O[sub 2]-resistant variant, underwent apoptosis on treatment with AlP with a similar delayed time course. The latter apoptosis was completely blocked by addition of L-lysine to the culture medium, which is the best substrate of AlP as LAO, indicating that decreased concentration of L-lysine in the culture medium by AlP treatment induced apoptosis. We also showed that the both apoptosis by AlP were associated with the release of cytochrome c from mitochondria and activation of caspase9, and overexpressed Bcl-2 could inhibit both of the AlPinduced apoptosis. These results indicate that AlP induces apoptosis in cells by two distinct mechanisms; one rapid and mediated by H[sub 2]O[sub 2], the other delayed and mediated by deprivation of L-lysine, both of which utilize caspase-9/ cytochrome c system. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
44. A sensitive radioimmunoassay for circulating α-interferon in the plasma of healthy children and patients with measles virus infection.
- Author
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Shiozawa, S., Yoshikawa, N., Iijima, K., and Negishi, K.
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- *
JUVENILE diseases , *YOUNG adults , *RADIOIMMUNOASSAY , *INTERFERONS , *ANTINEOPLASTIC agents , *MEASLES virus - Abstract
The mean circulating α-interferon of healthy children aged 2 to 13.5 yrs as measured by a radioimmunoassay was 0.119 ± 0.031 ng/ml, which was significantly tower than that of young adults. Circulating α-interferon of children with measles virus infection aged 1 to 11 yrs, on their first visit to the hospital when they were fully symptomatic, was 0.095 ± 0.035 ng/ml (n = 39). It was 0.105 ± 0.070 ng/ml (n = 21) on their second visit, 7 to 10 days after their first visit when the patients were convalescent. The difference was statistically insignificant. It is concluded that immunoreactive circulating a-interferon is low in children and reaches maximum level in young adults, subsequently declining gradually with age. Immunoreactive circulating a-interferon, a possible reflection of endogenous a-interferon. does not change significantly by the infection of measles virus. [ABSTRACT FROM AUTHOR]
- Published
- 1988
45. Leukemic cells with 11q23 translocations express granulocyte colony-stimulating factor (G-CSF) receptor and their proliferation is stimulated with G-CSF.
- Author
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Inukai, T, Sugita, K, Iijima, K, Goi, K, Tezuka, T, Kojika, S, Kagami, K, Mori, T, Kinoshita, A, Suzuki, T, O-Koyama, T, and Nakazawa, S
- Subjects
- *
LYMPHOBLASTIC leukemia , *CHROMOSOMAL translocation , *GRANULOCYTE-colony stimulating factor , *ANTINEOPLASTIC agents , *LYMPHOBLASTIC leukemia treatment , *B cells , *CELL division , *CELL lines , *CELL receptors , *CHROMOSOMES , *DNA , *ETOPOSIDE , *GENE mapping , *GRANULOCYTES , *IMMUNOPHENOTYPING , *CHRONIC myeloid leukemia , *CYTARABINE , *MITOXANTRONE , *CANCER cell culture , *BLOOD , *THERAPEUTICS - Abstract
We report a 20-month-old boy with acute lymphoblastic leukemia with the 11q23 translocation whose blasts markedly increased in peripheral blood after intravenous granulocyte colony-stimulating factor (G-CSF) administration, but disappeared after stopping G-CSF. The in vitro study showed that the leukemic cells separated from this patient expressed G-CSF receptor (G-CSFR) and an addition of G-CSF stimulated their proliferation by 3H-thymidine incorporation assay (stimulation index, 4.9). To clarify whether or not leukemic cells with 11q23 translocations generally express G-CSFR and show proliferative response to G-CSF, we performed the similar in vitro experiments using eight leukemic cell lines with 11q23 translocations. We found that all cell lines examined expressed G-CSFR (20-98%) and proliferation of seven leukemic cell lines was significantly enhanced in response to G-CSF (stimulation index >1.5 in five cell lines), suggesting a possible participation of the G-CSF/G-CSFR interaction in the process of growth regulation of leukemic cells with 11q23 translocations. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
46. EP-1403 Retrospective evaluation of usefulness of MR-guided adaptive radiotherapy of gastric MALT lymphoma.
- Author
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Okuma, K., Okamoto, H., Iijima, K., Nishioka, F., Kashihara, T., Shima, S., Uematsu, M., Igaki, H., Nakayama, Y., Itami, J., Murakami, N., and Nakamura, S.
- Subjects
- *
MUCOSA-associated lymphoid tissue lymphoma , *RADIOTHERAPY , *EVALUATION - Published
- 2019
- Full Text
- View/download PDF
47. Serious laryngeal edema during endoscopic resection for squamous cell carcinoma of the esophagus.
- Author
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Ara, N., Uno, K., Iijima, K., Koike, T., Asano, N., and Shimosegawa, T.
- Subjects
- *
HEAD & neck cancer , *LARYNX - Abstract
The detection of early esophageal squamous cell carcinoma (ESCC) in patients following radiotherapy for squamous cell carcinoma of the head and neck (HNSCC) has increased with the development of endoscopic technologies. The aim of the current case-control study was to elucidate the risk factors of serious laryngeal edema, a lethal complication that occurs during endoscopic resection for ESCC. Among 184 consecutive patients who were treated by endoscopic resection for ESCC between January 2009 and May 2012, five of 22 patients with a history of radiotherapy for HNSCC suffered from serious laryngeal edema, which was not observed in patients who had not undergone radiotherapy. The susceptibility to serious laryngeal edema in patients with a history of radiotherapy followed by neck dissection for HNSCC was significantly greater than those without such histories. Despite the limited number of cases, we suggest that previous radiotherapy followed by neck dissection for HNSCC might be a predictive factor for serious laryngeal edema during endoscopic resection. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
48. In situ growth of superconducting Nd-Ce-Cu-O thin films.
- Author
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Terashima, T., Bando, Y., Iijima, K., Yamamoto, K., Hirata, K., Hayashi, K., Matsuda, Y., and Komiyama, S.
- Subjects
- *
THIN films , *COPPER oxide superconductors , *EPITAXY , *STRONTIUM compounds , *EVAPORATION (Chemistry) - Abstract
Superconducting Nd-Ce-Cu-O thin films were epitaxially grown on SrTiO3 (100) by activated reactive evaporation. As-grown films showed the metallic temperature dependence of the resistivity and superconducting transition at 12.5 K (R=0). The remarkable parallel shift of the onset temperature of the resistive transition in the magnetic fields was observed. Ginzburg–Landau coherence lengths along the c axis and in the basal plane are 7 and 96 Å, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 1990
- Full Text
- View/download PDF
49. Tunneling measurements on superconductor/insulator/superconductor junctions using single-crystal YBa2Cu3O7-x thin films.
- Author
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Hirata, K., Yamamoto, K., Iijima, K., Takada, J., Terashima, T., Bando, Y., and Mazaki, H.
- Subjects
- *
THIN films , *COPPER oxide superconductors , *HIGH temperature superconductors - Abstract
We have, for the first time, made quasi-particle tunneling measurements on a YBa2Cu3O7-x(001)/Y2O3 (001)/YBa2 Cu3 O7-x (001)junction, which was epitaxially grown on a MgO(100) substrate in an in-situ process. Both layers of YBa2 Cu3 O7-x showed the same superconducting transition of Tc end =86 K with ΔT(R=10–90%)=1.5 K. Quasi-particle tunneling in the direction perpendicular to the Cu-O planes was measured. A gap parameter Δ(4.5 K) of 9.0±0.2 meV and a value of 2Δ/kTc of 3.5+0.4-0.6 were obtained. [ABSTRACT FROM AUTHOR]
- Published
- 1990
- Full Text
- View/download PDF
50. Epitaxial growth of YBa2Cu3O7-x thin films on (110) SrTiO3 single crystals by activated reactive evaporation.
- Author
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Terashima, T., Bando, Y., Iijima, K., Yamamoto, K., and Hirata, K.
- Subjects
- *
YTTRIUM , *METALLIC films , *STRONTIUM compounds , *CRYSTALLIZATION - Abstract
The orientation of YBa2Cu3O7-x thin films grown on (110) planes of SrTiO3 by activated reactive evaporation was investigated by means of reflection high-energy electron diffraction. The orientation of the films depended on the substrate temperature. The films with (110) planes parallel to the substrate surface grew in a narrow range of substrate temperatures around 530 °C, while the films with (103) planes parallel to the surface grew at temperatures above 600 °C. The change of the epitaxial orientation with the substrate temperature is discussed in terms of the temperature dependence of the lattice mismatch between YBa2Cu3O7-x and SrTiO3. [ABSTRACT FROM AUTHOR]
- Published
- 1988
- Full Text
- View/download PDF
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