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Cyclooxygenase 2 1195G〉A polymorphism is associated with chronic obstructive pulmonary disease in Japanese and Chinese patients

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Chinese Medical Journal 2013年第12期126卷 2215-2221页

作者： CHEN Li-jun XU Wang Yasuyuki Taooka Miki Ohe hitoshi takahashi Akihisa Sutani Takashige Kuraki Takeshi Isobe Department of Internal Medicine Division of Clinical Oncology & Respiratory Medicine Shimane University Faculty of Medicine 89-1 Enya cho Izumo Shimane 6938501 Japan Department of Respiratory Medicine Second Affiliated Hospitalof Ning Xia Medical University Yinchuan Ningxia 750001 China Department of Dermatology Shimane University Faculty of Medicine 89-1 Enyacho Izumo Shimane 6938501 Japan

Background Cyclooxygenase-2 （COX-2） is overexpressed during airway inflammation in chronic obstructive pulmonary disease （COPD） patients.Single nucleotide polymorphisms （SNPs） in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to COPD.We investigated the association between COX-2 （-765G〉C,-1195G〉A） polymorphisms and COPD susceptibility in Japanese and Chinese patients.Methods COX-2 genotypes were determined by polymerase chain reaction,restriction fragment length polymorphism in 230 COPD patients （103 Japanese and 127 Chinese） and 273 healthy controls （129 Japanese and 144 Chinese）.Results The frequency of-1195AA homozygote was significantly higher than the controls in Chinese COPD （adjusted OR=2.43,95% CI 1.14-4.19）,Japanese COPD （adjusted OR=-2.25,95% Cl 1.06-4.76） and combined COPD groups （adjusted OR=2.26,95% CI 1.34-3.99）.There was no difference in COX-2-765G〉C polymorphism between COPD and control groups in either Japanese or Chinese,while more Chinese individuals carried the-765C allele than Japanese in both groups （15.3% vs.2.9% in COPD,18.8% vs.5.5% in control）.Chinese individuals with the haplotype-765G：-1195A were at higher risk for COPD （adjusted OR=1.93,95% CI 1.05-3.55）.Conclusions The COX-2-1195AA genotype is associated with increased risk for COPD in both Japanese and Chinese individuals.Although COX-2-765G〉C polymorphism was not associated with COPD in either ethnic group,the-765C allele frequency was higher in Chinese than Japanese and haplotype-765G-1195A may confer susceptibility to COPD in Chinese.

关键词： cyclooxygenase-2 polymorphisms chronic obstructive pulmonary disease Japanese, Chinese

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Pituitary intratumoral hemorrhage during radiation therapy following partial removal of giant pituitary adenoma: A case report

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Case Reports in Clinical Medicine 2014年第1期3卷 38-41页

作者： Junyang Liu Yuichiro Yoneoka Kensuke Tanaka Hiraku Satou Eisuke Abe Naoto Watanabe Yukihiko Fuji hitoshi takahashi Hidefumi Aoyama Department of Neurosurgery Brain Research Institute Niigata University Niigata Japan Department of Pathology Brain Research Institute Niigata Uni-versity Niigata Japan Department of Radiology Niigata University Graduate School of Medical and Dental Sciences Niigata Japan

We report a rare case of intratumoral hemorrhage during postoperative radiotherapy for pituitary adenoma. A 57-year-old Asian male, complaining of long-standing eye strain, underwent a medical checkup of the brain. Magnetic resonance imaging showed a multicystic giant pituitary adenoma. The patient underwent an endoscopic endonasal transsphenoidal partial removal of the adenoma to provide optic pathway decompression and got relief from the visual symptoms. Just before completion of the postoperative radiotherapy for residual adenoma, the patient developed right hemiparesis, mild motor aphasia, and right oculomotor palsy. A cranial CT scan showed intratumoral hemorrhage into the intratumoral cyst. The patient therefore had to undergo three additional craniotomies for evacuation of cyst contents over the next 8 months. The follow-up MRI at 11 months after the initial hemorrhage showed that the new oozing of blood in the intratumoral cyst was still appearing. Intratumoral hemorrhage is a rare, albeit life-threatening, complication of pituitary adenoma. We reviewed relevant literature and suggested that the cystic component in pituitary adenoma could be a key pathogenesis of this rare complication. In conclusion, we suggest that it may be necessary to realize that cases which have cystic giant pituitary adenoma may cause hemorrhage by chance with the foreseeability.

关键词： Pituitary Hemorrhage Pituitary Adenoma Radiotherapy Cyst Giant

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New Level-Shift LDMOS Structure for a 600 V-HVIC on Thick SOl

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Journal of Energy and Power Engineering 2012年第9期6卷 1515-1520页

作者： Masaharu Yamaji Keisei Abe Akihiro Jonishi Hidenori takahashi hitoshi Sumida Fuji Electric Co. Ltd. Matsumoto Nagano 390-0821 Japan

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Immunological effect of local ablation combined with immunotherapy on solid malignancies

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Chinese Journal of Cancer 2017年第6期36卷 252-257页

作者： Yusuke takahashi Noriyuki Matsutani Takashi Nakayama hitoshi Dejima Hirofumi Uehara Masafumi Kawamura Department of General Thoracic Surgery Teikyo University School of Medicine

Recent comprehensive investigations clarified that immune microenvironment surrounding tumor cells are deeply involved in tumor progression,metastasis,and response to treatment.Furthermore,several immunotherapeutic trials have achieved successful results,and the immunotherapeutic agents are available in clinical practice.To enhance their demonstrated efficacy,combination of immunotherapy and ablation has begun to emerge.Local ablations have considerable advantages as an alternative therapeutic option,especially its minimal invasiveness.In addition,local ablations have shown immune-regulatory effect in preclinical and clinical studies.Although the corresponding mechanisms are still unclear,the local ablations combined with immunotherapy have been suggested in the treatment of several solid malignancies.This article aims to review the published data on the immune-regulatory effects of local ablations including stereotactic body radiotherapy,cryoablation,radiofrequency ablation,and high-intensityfocused ultrasound.We also discuss the value of local ablations combined with immunotherapy.Local ablations have the potential to improve future patient outcomes;however,the effectiveness and safety of local ablations combined with immunotherapy should be further investigated.

关键词：免疫治疗剂免疫效应实体瘤免疫调节作用高强度聚焦超声肿瘤细胞临床实践综合调查

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Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

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World Journal of Gastroenterology 2012年第38期18卷 5360-5368页

作者： Kunihiro Hosono Eiji Yamada Hiroki Endo Hirokazu takahashi Masahiko Inamori Yoshitaka Hippo hitoshi Nakagama Atsushi Nakajima Division of Gas-troenterology Yokohama City University School of Medicine Yokohama 2360004 Japan Division of Cancer Development System National Cancer Center Research Institute Tokyo 1040045 Japan

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis.

关键词：肿瘤坏死因子受体肠腺人类 caspase-3 血清浓度共聚焦显微镜免疫组化 c-Jun

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Early gastric cancer frequently has high expression of KKLC-1, a cancer-testis antigen

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World Journal of Gastroenterology 2017年第46期23卷 8200-8206页

作者： Nobue Futawatari Takashi Fukuyama Rui Yamamura Akiko Shida Yoshihito takahashi Yatsushi Nishi Yoshinobu Ichiki Noritada Kobayashi hitoshi Yamazaki Masahiko Watanabe Department of Surgery Sagamihara National Hospital Division of Biomedical Research Kitasato University Medical Center Department of Surgery School of MedicineKitasato University Department of Surgery Kitasato University Medical Center Second Department of Surgery School of MedicineUniversity of Occupational and Environmental Health Department of Pathology Kitasato University Medical Center

AIM To assess cancer-testis antigens(CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.METHODS Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1(KK-LC-1), melanoma antigen(MAGE)-A1, MAGE-A3 and New York esophageal cancer-1(NYESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. RESULTS The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion(MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion(MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage(36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NYESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1(MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). CONCLUSION The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

关键词： Cancer-testis antigen Kitakyushu lung cancer antigen-1 Melanoma antigen-A1 Melanoma antigen-A3 Gastric cancer New York esophageal cancer-1 Clinicopathological factor early stage

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Investigation of Experimental Con6guration for Electron Bernstein Wave Heating on LHD

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Plasma Science and Technology 2009年第4期11卷 430-438页

作者： Hiroe IGAMI Ryosuke IKEDA Hiromi takahashi Yasuo YOSHIMURA Takashi SHIMOZUMA Shin KUBO hitoshi TANAKA Kazunobu NAGASAKI Takashi MUTOH the LHD Experiment Group National Institute for Fusion Science 509-5292 Toki Japan Graduate School of Energy Science Kyoto University 606-8502 Kyoto Japan Institute of Advanced Energy Kyoto University 611-0011 Uji Japan

Investigation of experimental configuration for the electron Bernstein wave （EBW） heating by using the existing electron cyclotron heating （ECH） antennas on LHD was performed. By using an antenna installed in the lower port, direct oblique launching of the extraordinary （X-） mode from the high magnetic field side （HFS） is available. Since the parallel component of the refractive index （NIF） varies during propagation because of the inhomogeneity of the magnetic field, NH can be zero when the launched X-mode crosses the fundamental electron cyclotron resonance （ECR） layer even NⅡ is noonzero initially. In such a condition, if the electron density is above a certain level the obliquely launched X-mode can pass the fundamental ECR layer without being damped out and can be mode-converted to EBW that is absorbed at the Doppler shifted ECR layer. By using an antenna installed in the horizontal port, oblique launching from the lower magnetic field side （LFS） toward the over-dense plasma is available. Excitation of EBW via the mode conversion process of ordinary mode（O）-extraordinary mode（X）-electron Bernstein wave （B） is expected with the O-mode launching toward an appropriate direction. The O-X-B mode conversion rate and the region of power deposition were surveyed by varying the magnetic field strength and the launching direction. The results of the survey suggest that efficient heating in the core region is difficult by using the existing antenna. Rearrangement of the final mirror of the launching antenna may be needed.

关键词： LHD electron cyclotron heating （ECH） electron Bernstein wave （EBW）,high density plasma

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Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers

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World Journal of Gastroenterology 2020年第4期26卷 424-432页

作者： Akiko Shida Takashi Fukuyama Nobue Futawatari Haruki Ohmiya Yoshinobu Ichiki Tetsuro Yamashita Yatsushi Nishi Noritada Kobayashi hitoshi Yamazaki Masahiko Watanabe Yoshihito takahashi Division of Pathology Kitasato UniversitySagamiharaKanagawa 252-0374Japan Division of Biomedical Research Kitasato University Medical CenterKitamotoSaitama 364-8501Japan Division of Surgery Toho UniversityOhashi Medical CenterMegurokuTokyo 153-8515Japan Department of Biological Chemistry and Food Sciences Faculty of AgricultureIwate UniversityMoriokaIwate 020-8505Japan Division of Surgery Kitasato University Medical CenterKitamotoSaitama 364-8501Japan Division of Pathology Kitasato University Medical CenterKitamotoSaitama 364-8501Japan Division of Surgery Kitasato UniversitySagamiharaKanagawa 252-0374Japan

BACKGROUND The ABCD stratification[combination of serum pepsinogen(PG)levels and titers of antibody(immunoglobulin G,IgG)against Helicobacter pylori(H.pylori)]is effective for the classification of individuals at risk of developing gastric cancer(GC).The Kita–Kyushu lung cancer antigen-1(KK-LC-1)is a Cancer/Testis antigen frequently expressed in GC.AIM To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC.METHODS We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors.The levels of serum PG I/PG II and IgG against H.pylori were measured.According to their serological status,the patients were classified into the four groups of the ABCD stratification.RESULTS Of the 77 examined patients,63(81.8%)expressed KK-LC-1.The IgG titers of H.pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1(P=0.0289 and P=0.0041,respectively).The expression of KK-LC-1 in group C[PG method(+)/H.pylori infection(+)]was as high as 93.9%high.KK-LC-1 was also detected in group A[-/-].CONCLUSION The KK-LC-1 expression in GC was associated with H.pylori infection and atrophic status,so that,KK-LC-1 may be a useful marker for the diagnosis of GC.

关键词： Gastric cancer Tumor antigen Cancer/testis antigen Kita–Kyushu lung cancer antigen-1 Helicobacter pylori Early detection of cancer

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Reversed portal flow: Clinical influence on the long-term outcomes in cirrhosis

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World Journal of Gastroenterology 2015年第29期21卷 8894-8902页

作者： Takayuki Kondo hitoshi Maruyama Tadashi Sekimoto Taro Shimada Masanori takahashi Osamu Yokosuka Department of Gastroenterology and Nephrology Graduate School of Medicine Chiba University

AIM: To elucidate the natural history and the longitudinal outcomes in cirrhotic patients with non-forward portal flow(NFPF).METHODS: The present retrospective study consisted of 222 cirrhotic patients(120 males and 102 females; age, 61.7 ± 11.1 years). The portal hemodynamics were evaluated at baseline and during the observation period using both pulsed and color Doppler ultrasonography. The diameter(mm), flow direction, mean flow velocity(cm/s), and mean flow volume(m L/min) were assessed at the portal trunk, the splenic vein, the superior mesenteric vein, and the collateral vessels. The average values from 2 to 4 measurements were used for the data analysis. The portal flow direction was defined as follows: forward portal flow(FPF) for continuous hepatopetal flow; bidirectional flow for to-and-fro flow; and reversed flow for continuous hepatofugal flow. The bidirectional flow and the reversed flow were classified as NFPF in this study. The clinical findings and prognosis were compared between the patients with FPF and those with NFPF. The median follow-up period was 40.9 mo(range, 0.3-156.5 mo).RESULTS: Twenty-four patients(10.8%) demonstrated NFPF, accompanied by lower albumin level, worse ChildPugh scores, and model for end-stage liver disease scores. The portal hemodynamic features in the patients with NFPF were smaller diameter of the portal trunk;presence of short gastric vein, splenorenal shunt, or inferior mesenteric vein; and advanced collateral vessels(diameter > 8.7 mm, flow velocity > 10.2 cm/s, and flow volume > 310 m L/min). The cumulative incidence rates of NFPF were 6.5% at 1 year, 14.5% at 3 years, and 23.1% at 5 years. The collateral vessels characterized by flow velocity > 9.5 cm/s and those located at the splenic hilum were significant predictive factors for developing NFPF. The cumulative survival rate was significantly lower in the patients with NFPF(72.2% at 1 year, 38.5% at 3 years, 38.5% at 5 years) than in those with forward portal flow(84.0% at 1 year, 67.8% at 3 years, 54.3% at 5 yea

关键词： Non-forward portal flow Reversed portalflow Cirrhosis Doppler ultrasound Portal hemodynamics

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FAULTING-INDUCED PERMEABILITY CHANGE IN SHIRAHAMA SANDSTONE AND IMPLICATION FOR CO_2 AQUIFER STORAGE

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岩石力学与工程学报 2003年第6期22卷 995-1001页

作者： LiXiaochun takahashiManabu WuZhishen Koidehitoshi OhsumiTakashi CO2StorageResearchGroup ResearchInnovativeTechnologyfortheEarthKyoto619-0292Japan ResearchCenterforDeepGeologicalEnvironments AISTTsukuba605-8567Japan DepartmentofCivilandUrbanEngineering IbarakiUniversityHitachi316-0033Japan

The long-term safety assessment of CO2 aquifer storage requires a deep understanding o permeability evolution during inelastic deformations in sedimentary rocks.The permeability change has been measured in the entire process from elastic,plastic,post-failure to axial stress unloading for Shirahama sandstone subjected to triaxial compressions under various confining pressures.The measurements revealed that the confining pressure plays an important role in controlling inelastic deformation behavior and the tendency of the permeability evolution.In the brittle faulting regime under a low confining pressure,significant increase in permeability accompanied by dilatancy can be observed.In brittle-ductile transition regime and ductile regime,faulting or inelastic deformation does not necessarily and significantly enhance the permeability,and the permeability during deformation is lower than their corresponding initial values.Microscopic observations revealed that the two mechanisms:(1)shear-enhanced cracking,and (2)grain crushing,are responsible for these inelastic deformation and permeability evolution tendency.The presented results suggested that storing CO2 in those sites where ductile deformation prevails may be more safe.

关键词： CO2 砂岩渗透含水层隔离

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