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| 1 | SMALL ORGAN SIZE 1 and SMALL ORGAN SIZE 2/DWARF AND LOW-TILLERING Form aComplex to Integrate Auxin and Brassinosteroid Signaling in Rice显示文摘尽管植物生长素和 brassinosteroid (BR ) synergistically 控制各种各样的植物回答,位于 auxin-BR 串音下面的分子的机制很好没被理解。我们以前识别了 SMOS1,一个调整植物生长素的 APETALA2 类型抄写因素,作为小机关的原因的基因缩放 1 (smos1 ) 被各种各样的机关的一种减少的最后的尺寸在米饭描绘的异种。在这研究,我们识别了另一 smos 异种, smos2,哪个表演与 smos1 难区分的显型。SMOS2 与以前报导的矮子和 LOW-TILLERING (DLT ) 相同,它编码涉及 BR 发信号的 GRAS 蛋白质。SMOS1 和 SMOS2/DLT 身体上交往合作地在酵母并且在米饭原子核提高 transcriptional transactivation 活动。一致地, OsPHI-1 的表示, SMOS1 的一个直接目标,当 SMOS1 和 SMOS2/DLT 蛋白质两个都是在米饭房间的现在时,仅仅是 upregulated。一起拿,我们的结果建议 SMOS1 和 SMOS2/DLT 在在米饭表明串音的 auxin-BR 上形成重点建筑群。 | Ko Hirano Hideki Yoshida Koichiro Aya Mayuko Kawamura Makoto Hayashi Tokunori Hobo Karma Sato-lzawa Hidemi Kitano Miyako Ueguchi-Tanaka Makoto Matsuoka | 2017 | Molecular Plant2017，10，4： | 20 |
| 2 | 奥斯特/GPS掩星与地面雷达联合观测电离层电子密度的初步结果显示文摘1999年2月丹麦发射了一颗奥斯特小卫星,它装载了两台GPS接收机,其中一台用于电离层和中性大气掩星测量,另一台用于自主定位。本文给出了1999年10月奥斯特/GPS掩星与日本MU雷达和数字测高仪的联合观测结果。奥斯特掩星反演得到的电子密度剖面与地面雷达观测的进行了比较,结果表明:天基和地基雷达观测的电子密度是一致的。文章还给出利用GPS的单频信号反演电离层电子密度剖面技术和3维射线追踪技术模拟掩星结果。 | 张训械 P.Hoeg G.B.Larsen Stig Syndergaard Martin B.S Jakob G.R S.Fukao Kiyoshi lgarashi Seiji Kawamura | 2000 | 全球定位系统2000，25，3： | 18 |
| 3 | Sentinel lymph node navigation surgery for early stage gastric cancer显示文摘We attempted to evaluate the history of sentinel node navigation surgery(SNNS),technical aspects,tracers,and clinical applications of SNNS using Infrared Ray Electronic Endoscopes(IREE)combined with Indocyanine Green(ICG).The sentinel lymph node(SLN)is defined as a first lymph node(LN)which receives cancer cells from a primary tumor.Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s.Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan.Kitagawa et al reported that the endoscopic dual(dye and radioisotope)tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer(EGC).We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer,combined with IREE(Olympus Optical,Tokyo,Japan)to detect SLN.LN metastasis rate of EGC is low.Hence,clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection,which could preserve the patient’s quality of life after operation.The most ideal method of SNNS should allow secure and accurate detection of SLN,and real time observation of lymphatic flow during operation. | Norio Mitsumori Hiroshi Nimura Naoto Takahashi Masahiko Kawamura Hiroaki Aoki Atsuo Shida Nobuo Omura Katsuhiko Yanaga | 2014 | World Journal of Gastroenterology2014，20，19： | 15 |
| 4 | Nutritional status in relation to lifestyle in patients with compensated viral cirrhosis显示文摘AIM:To assess the nourishment status and lifestyle of non-hospitalized patients with compensated cirrhosis by using noninvasive methods.METHODS:The subjects for this study consisted of 27 healthy volunteers,59 patients with chronic viral hepatitis,and 74 patients with viral cirrhosis,from urban areas.We assessed the biochemical blood tests,anthropometric parameters,diet,lifestyle and physical activity of the patients.A homeostasis model assessment-insulin resistance(HOMA-IR) value of ≥ 2.5 was considered to indicate insulin resistance.We measured height,weight,waist circumference,arm circumference,triceps skin-fold thickness,and handgrip strength,and calculated body mass index,arm muscle circumference(AMC),and arm muscle area(AMA).We interviewed the subjects about their dietary habits and lifestyle using health assessment computer software.We surveyed daily physical activity using a pedometer.Univariate and multivariate logistic regression modeling were used to identify the relevant factors for insulin resistance.RESULTS:The rate of patients with HOMA-IR ≥ 2.5(which was considered to indicate insulin resistance) was 14(35.9%) in the chronic hepatitis and 17(37.8%) in the cirrhotic patients.AMC(%)(control vs chronic hepatitis,111.9% ± 10.5% vs 104.9% ± 10.7%,P = 0.021;control vs cirrhosis,111.9% ± 10.5% vs 102.7% ± 10.8%,P = 0.001) and AMA(%)(control vs chronic hepatitis,128.2% ± 25.1% vs 112.2% ± 22.9%,P = 0.013;control vs cirrhosis,128.2% ± 25.1% vs 107.5% ± 22.5%,P = 0.001) in patients with chronic hepatitis and liver cirrhosis were significantly lower than in the control subjects.Handgrip strength(%) in the cirrhosis group was significantly lower than in the controls(control vs cirrhosis,92.1% ± 16.2% vs 66.9% ± 17.6%,P < 0.001).The results might reflect a decrease in muscle mass.The total nutrition intake and amounts of carbohydrates,protein and fat were not significantly different amongst the groups.Physical activity levels(kcal/d)(control vs cirrhosis,210 ± 113 kcal/d vs 125 ± 74 kcal/d,P = 0.001),number of steps(step/d)(control vs cirrhosis,8070 ±3027 step/d vs 5789 ± 3368 step/d,P = 0.011),and exercise(Ex)(Ex/wk)(control vs cirrhosis,12.4 ± 9.3 Ex/wk vs 7.0 ± 7.7 Ex/wk,P = 0.013) in the cirrhosis group was significantly lower than the control group.The results indicate that the physical activity level of the chronic hepatitis and cirrhosis groups were low.Univariate and multivariate logistic regression modeling suggested that Ex was associated with insulin resistance(odds ratio,6.809;95% CI,1.288-36.001;P = 0.024).The results seem to point towards decreased physical activity being a relevant factor for insulin resistance.CONCLUSION:Non-hospitalized cirrhotic patients may need to maintain an adequate dietary intake and receive lifestyle guidance to increase their physical activity levels. | Fumikazu Hayashi Chika Momoki Miho Yuikawa Yuko Simotani Etsushi Kawamura Atsushi Hagihara Hideki Fujii Sawako Kobayashi Shuji Iwai Hiroyasu Morikawa Masaru Enomoto Akihiro Tamori Norifumi Kawada Satoko Ohfuji Wakaba Fukusima Daiki Habu | 2012 | World Journal of Gastroenterology2012，18，40： | 11 |
| 5 | Development of underground mine monitoring and communication system integrated ZigBee and GIS显示文摘An automated underground mine monitoring and communication system based on the integration of new technologies is introduced to promote safety and health,operational management and cost-effectiveness.The proposed system integration considering Wireless Sensor Network(WSN) assisted Geographic Information System(GIS) enables to monitor and control underground mining applications from surface office.Based on the capabilities of WSNs,ZigBee network is adapted for near real-time monitoring,ventilation system control and emergency communication in underground mine.ZigBee nodes were developed to sense environmental attributes such as temperature,humidity and gases concentration;switching ON and OFF ventilation fans;and texting emergency messages.A trigger action plan for monitored attributes above normal and threshold value limits is programmed in the surface GIS management server.It is designed to turn the auxiliary fans on remotely or automatically in orange condition and sending evacuation messages for underground miners in unsafe(red) condition.Multi-users operation and 3D visualisations are other successful achievements of the proposed system for the underground monitoring and communication. | Moridi Mohammad Ali Kawamura Youhei Sharifzadeh Mostafa Chanda Emmanuel Knox Wagner Markus Jang Hyongdoo Okawa Hirokazu | 2015 | International Journal of Mining Science and Technology2015，25，5： | 11 |
| 6 | Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs显示文摘AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. | Hiroki Morita Erito Mochiki Nobuyuki Takahashi Kiyoshi Kawamura Akira Watanabe Toshinaga Sutou Atsushi Ogawa Mitsuhiro Yanai Kyoichi Ogata Takaaki Fujii Tetsuro Ohno Souichi Tsutsumi Takayuki Asao Hiroyuki Kuwano | 2013 | World Journal of Gastroenterology2013，19，39： | 9 |
| 7 | TIDAL FEATURES IN THE CHINA SEAS AND THEIR ADJACENT SEA AREAS AS DERIVED FROM TOPEX/POSEIDON ALTIMETER DATA显示文摘Some important tidal features of 8 major tidal constituents ( M 2, S 2, K 1, O 1, P 1, Sa, N 2 and K 2 ) in the China Seas and their adjacent sea areas were obtained using six years’ TOPEX/POSEIDON altimeter data. The results showed that the obtained co tidal and co range charts for these major tidal constituents agreed well with those of previous researches using observational data from coastal tidal gauge stations and numerical models. | 胡建宇 Hiroshi KAWAMURA 洪华生 Fumiaki KOBASⅢ 谢强 | 2001 | Chinese Journal of Oceanology and Limnology2001，19，4： | 9 |
| 8 | 改进移动最小二乘法及其在结构可靠性分析中的应用显示文摘基于移动最小二乘法的响应面法对结构可靠性问题进行分析.在确定样本点权重时,将样本点与中心点、响应面的距离同时作为判断其权重大小的依据,并考虑每次迭代得到的响应面函数对下一迭代的影响域的影响,由此提出改进移动最小二乘法.结果表明,改进方法可有效提高计算精度. | 韦益夫 KAWAMURA Yasumi 王德禹 | 2018 | 上海交通大学学报2018，52，4： | 9 |
| 9 | Hepatitis C virus enhances incidence of idiopathic pulmonary fibrosis显示文摘AIM: To investigate the cumulative development incidence and predictive factors for idiopathic pulmonary fibrosis in hepatitis C virus (HCV) positive patients. METHODS: We studied 6150 HCV infected patients who were between 40-70 years old (HCV-group). Another 2050 patients with hepatitis B virus (HBV) were selected as control (HBV-group). The mean observation period was 8.0 ± 5.9 years in HCV-group and 6.3 ± 5.5 years in HBV-group. The primary goal is the development of idiopathic pulmonary fibrosis (IPF) in both groups. The cumulative appearance rate of IPF and independent factors associated with the incidence rate of IPF were calculated using the Kaplan- Meier method and the Cox proportional hazard model. All of the studies were performed retrospectively by collecting and analyzing data from the patient records in our hospital. RESULTS: Fifteen patients in HCV-group developedIPF. On the other hand, none of the patients developed IPF in HBV-group. In HCV-group, the cumulative rates of IPF development were 0.3% at 10th year and 0.9% at 20th year. The IPF development rate in HCV-group was higher than that in HBV-group (P = 0.021). The IPF development rate in patients with HCV or HBV was high with statistical significance in the following cases: (1) patients ≥ 55 years (P < 0.001); (2) patients who had smoking index (package per day × year) of ≥ 20 (P = 0.002); (3) patients with liver cirrhosis (P = 0.042). CONCLUSION: Our results indicate that age, smoking and liver cirrhosis enhance the development of IPF in HCV positive patients. | Yasuji Arase Fumitaka Suzuki Yoshiyuki Suzuki Norio Akuta Masahiro Kobayashi Yusuke Kawamura Hiromi Yatsuji Hitomi Sezaki Tetsuya Hosaka Miharu Hirakawa Satoshi Saito Kenji Ikeda Hiromitsu Kumada | 2008 | World Journal of Gastroenterology2008，14，38： | 8 |
| 10 | Clinical significance of white gastric crypt openings observed via magnifying endoscopy显示文摘AIM:To evaluate the relationship between Helicobacter pylori(H.pylori)-induced gastritis and white gastric mucosal crypt openings(COs)in the gastric corpus.METHODS:A total of 175 consecutive patients(including 69 patients with gastric cancer)were enrolled in this study.We used magnifying endoscopy(ME)to observe the mucosa microsurface of the lesser and greater curvature of the gastric corpus(350 areas in all).We focused on areas with a round pit microstructure(primarily observed in non-atrophied areas)and evaluated the white openings of these gastric pits.We classified the whiteness of the COs as the'white-edged dark spot'type(consisting of a dark spot bordered by white);the'white'type(pure white with no dark spot);and the'dense white pit(DWP)'type(dense white,resembling a snowball).Gastritis was also histologically evaluated according to the updated Sydney System.RESULTS:We detected round COs using ME in 246 of the 350 areas examined.The histological examination showed significantly more mononuclear cells and neutrophil infiltration in the'white'and'DWP'types than the'white-edged dark spot'type(P<0.001).Furthermore,significantly high-grade inflammation and evidence of active H.pylori-induced gastritis was observed in the'DWP'type(P<0.001).Significant differences were observed in the whiteness of COs between H.pylori-positive(n=139)and negative(n=36)patients(P<0.001).The sensitivity and specificity of the'white'and'DWP'types for predicting H.pylori infection were78.5%and 81.7%,respectively.Of the patients with gastric cancer,22.5%(18/80)had'white-edged dark spots',51.3%(41/80)had'white'COs,and 26.3%(21/80)had'DWP'-type COs.'DWPs'were frequently observed among patients with undifferentiated gastric cancer[45.7%(16/35)].CONCLUSION:CO whiteness detected via ME was associated with histological evidence of gastritis and helps to predict the severity of inflammation and H.pyloriinduced activity. | Masashi Kawamura Hitoshi Sekine Shu Abe Daisuke Shibuya Katsuaki Kato Takayuki Masuda | 2013 | World Journal of Gastroenterology2013，19，48： | 7 |
| 11 | Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer显示文摘 | Shiro Oka Shinji Tanaka Iwao Kaneko Ritsuo Mouri Mayuko Hirata Toru Kawamura Masaharu Yoshihara Kazuaki Chayama | 2006 | Gastrointestinal Endoscopy2006，，6： | 6 |
| 12 | Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy显示文摘AIM: To clarify clinical features of the NSAID-induced small bowel lesions using a new method of endoscopy.METHODS: This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone doubleballoon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at Jichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient.RESULTS: Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively.The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug.CONCLUSION: NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon. | Yoshikazu Hayashi Hironori Yamamoto Hiroto Kita Keijiro Sunada Hiroyuki Sato Tomonori Yano Michiko Iwamoto Yutaka Sekine Tomohiko Miyata Akiko Kuno Takaaki Iwaki Yoshiyuki Kawamura Hironari Ajibe Kenichi Ido Kentaro Sugano | 2005 | World Journal of Gastroenterology2005，11，31： | 6 |
| 13 | Immunological effect of local ablation combined with immunotherapy on solid malignancies显示文摘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. | Yusuke Takahashi Noriyuki Matsutani Takashi Nakayama Hitoshi Dejima Hirofumi Uehara Masafumi Kawamura | 2017 | Chinese Journal of Cancer2017，36，6： | 6 |
| 14 | Long‐term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection显示文摘 | Tetsuya Hosaka Fumitaka Suzuki Masahiro Kobayashi Yuya Seko Yusuke Kawamura Hitomi Sezaki Norio Akuta Yoshiyuki Suzuki Satoshi Saitoh Yasuji Arase Kenji Ikeda Mariko Kobayashi Hiromitsu Kumada | 2013 | Hepatology2013，，： | 5 |
| 15 | 应力比对WC-Co硬质合金疲劳寿命及裂纹生长行为的影响(英文)显示文摘通过两种疲劳试验:旋转弯曲疲劳试验和3-或4-点弯曲疲劳试验测试细晶WC-Co硬质合金的裂纹生长行为和疲劳寿命。疲劳试验结果表明:所测试的大部分WC-Co硬质合金的疲劳寿命取决于裂纹生长周期。利用断裂力学基本方程推导出疲劳裂纹生长速率(da/dN)和最大应力强度因子(Kmax)的关系。根据此关系,获得材料的强度因子阈值(Kth)和疲劳断裂韧性值(Kfc)。基于修正的线性弹性断裂力学方程,对WC-Co硬质合金材料的疲劳寿命进行计算,疲劳寿命的计算结果与实验结果吻合较好。 | Hiroko MIKADO Sotomi ISHIHARA Noriyasu OGUMA Kenichi MASUDA Syo KITAGAWA Shingo KAWAMURA | 2014 | Transactions of Nonferrous Metals Society of China2014，24，S1： | 4 |
| 16 | Brown carbon in the cryosphere: Current knowledge and perspective显示文摘Recently, the light-absorbing organic carbon, i.e., brown carbon(Br C), has received an increasing attention, because they could significantly absorb the solar radiation in the range of short wavelengths rather than the purely scattering effect. Br C is ubiquitous in the troposphere. It could undergo long range transport within the atmospheric circulation. After the deposition on the surface of snow or ice in the cryospheric region, as the major light absorbing impurities with black carbon and dust, Br C could reduce the snow albedo and accelerate the glacier melting. In this context, this paper summarized the current knowledge of Br C(in aerosols and snow) in the cryospheric regions including the Arctic, Antarctic,and Alpines. Although some works have been conducted in those region, the current dataset on the optical properties of Br C like Absorption?ngstr€om Exponent(AAE) and Mass Absorption Efficiency(MAE) is still limited, which hampers stimulating an accurate evaluation of its climate effects. Especially in the Himalayas and Tibetan Plateau, where very limited information concerning Br C is available. Considering biomass burning as a dominant source of Br C, a large amount of emissions from biomass burning in South Asia could reach the Himalayas and Tibetan Plateau, where the climate effect of Br C merits more investigation in the future. | WU Guang-Ming CONG Zhi-Yuan KANG Shi-Chang Kimitaka KAWAMURA FU Ping-Qing ZHANG Yu-Lan WAN Xin GAO Shao-Peng LIU Bin | 2016 | Advances in Climate Change Research2016，7，1： | 4 |
| 17 | Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction显示文摘We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)- AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the 13C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to followup. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%,respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT. | Toshihiro Nishizawa Hidekazu Suzuki Takama Maekawa Naohiko Harada Tatsuya Toyokawa Toshio Kuwai Masanori Ohara Takahiro Suzuki Masahiro Kawanishi Kenji Noguchi Toshiyuki Yoshio Shinji Katsushima Hideo Tsuruta Eiji Masuda Munehiro Tanaka Shunsuke Katayama Norio Kawamura Yuko Nishizawa Toshifumi Hibi Masahiko Takahashi | 2012 | World Journal of Gastroenterology2012，18，21： | 4 |
| 18 | Shorting the defrost time on a heat-pump air conditioner显示文摘 | Kuwahara E Kawamura T Yamazaki M | 1985 | ASHRAE Transaction1985，91，1： | 3 |
| 19 | Long-term continuous entecavir therapy in nucleos(t)ide-na?ve chronic hepatitis B patients显示文摘 | Atsushi Ono Fumitaka Suzuki Yusuke Kawamura Hitomi Sezaki Tetsuya Hosaka Norio Akuta Masahiro Kobayashi Yoshiyuki Suzuki Satoshi Saitou Yasuji Arase Kenji Ikeda Mariko Kobayashi Sachiyo Watahiki Rie Mineta Hiromitsu Kumada | 2012 | Journal of Hepatology2012，，3： | 3 |
| 20 | Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars显示文摘New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting intracellularly.Mycobacteria have a unique cell wall.Deletion of the gene for arylamine N-acetyltransferase(NAT)decreases mycobacterial cell wall lipids,particularly the distinctive mycolates,and also increases antibiotic susceptibility and killing within macrophage of Mycobacterium bovis BCG.The nat gene and its associated gene cluster are almost identical in sequence in M.bovis BCG and M.tuberculosis.The gene cluster is essential for intracellular survival of mycobacteria.We have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT activity.Here,we characterize one class of such molecules—triazoles—in relation to its effects on the target enzyme and on both M.bovis BCG and M.tuberculosis.The most potent triazole mimics the effects of deletion of the nat gene on growth,lipid disruption and intracellular survival.We also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth,and use ligand-protein analysis to give further insight into the structure-activity relationships.We conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved. | Isaac M.Westwood Sanjib Bhakta Angela J.Russell Elizabeth Fullam Matthew C.Anderton Akane Kawamura Andrew W.Mulvaney Richard J.Vickers Veemal Bhowruth Gurdyal S.Besra Ajit Lalvani Stephen G.Davies Edith Sim | 2010 | Protein & Cell2010，1，1： | 3 |
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