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991.
Takashi Hashimoto Keiko Baba Kae Inoue Miyako Okane Satoshi Hata Takao Shishido Akira Naito Steffen Wildum Shinya Omoto 《Influenza and other respiratory viruses》2021,15(3):389
BackgroundBaloxavir marboxil (BXM) is an approved drug that selectively targets cap‐dependent endonuclease on PA subunit in the RNA polymerase complex of influenza A and B viruses. Amino acid substitutions at position 38 in the PA subunit were identified as a major pathway for reduced susceptibility to baloxavir acid (BXA), the active form of BXM. Additionally, substitutions found at positions E23, A37, and E199 in the PA subunit impact BXA susceptibility by less than 10‐fold.MethodsWe comprehensively evaluated the impact of novel amino acid substitutions identified in PA, PB1, and PB2 subunits in BXM clinical trials and influenza sequence databases by means of drug susceptibility and replicative capacity.ResultsPA/I38N in A(H1N1)pdm09 and PA/I38R in A(H3N2) were newly identified as treatment‐emergent substitutions in the CAPSTONE‐2 study. The I38N substitution conferred reduced susceptibility by 24‐fold, whereas replicative capacity of the I38N‐substituted virus was impaired compared with the wild‐type. The I38R‐substituted virus was not viable in cell culture. All other mutations assessed in this extensive study did not significantly affect BXA susceptibility (< 2.4‐fold change).ConclusionThese results provide additional information on the impact of amino acid substitutions in the trimeric viral polymerase complex to BXA susceptibility and will further support influenza surveillance. 相似文献
992.
Masakazu Yamamoto Masahiro Yoshida Junji Furuse Keiji Sano Masayuki Ohtsuka Shingo Yamashita Toru Beppu Yukio Iwashita Keita Wada Takako Eguchi Nakajima Katsunori Sakamoto Koichi Hayano Yasuhisa Mori Koji Asai Ryusei Matsuyama Teijiro Hirashita Taizo Hibi Nozomu Sakai Tsutomu Tabata Hisato Kawakami Hiroyuki Takeda Takuro Mizukami Masato Ozaka Makoto Ueno Yoichi Naito Naohiro Okano Takayuki Ueno Susumu Hijioka Satoru Shikata Tomohiko Ukai Steven Strasberg Michael G. Sarr Palepu Jagannath Tsann‐Long Hwang Ho‐Seong Han Yoo‐Seok Yoon Hee Jung Wang Shao‐Ciao Luo Ren Adam Mariano Gimenez Olivier Scatton Do‐Youn Oh Tadahiro Takada 《Journal of hepato-biliary-pancreatic sciences》2021,28(1):1-25
993.
Yamada Kaori Kozawa Nana Nagano Hitomi Fujita Masato Yamada Kei 《Abdominal imaging》2019,44(4):1261-1268
Abdominal Radiology - We report four patients with mucinous adenocarcinoma of the prostate, focusing on their magnetic resonance imaging (MRI) findings. The lesions appeared hyperintense on... 相似文献
994.
Kohsuke Hagisawa Manabu Kinoshita Masato Takikawa Shinji Takeoka Daizoh Saitoh Shuhji Seki Hiromi Sakai 《Transfusion》2019,59(10):3186-3196
995.
Noriko Nakanishi Ryohei Nomoto Kanako Sato Chihiro Koike Mari Kusuki Tatsuya Nakamura Katsumi Shigemura Toshiro Shirakawa Masato Fujisawa Issei Tokimatsu Kayo Osawa 《Journal of infection and chemotherapy》2019,25(2):154-156
Pseudomonas aeruginosa, responsible for serious nosocomial-acquired infections, possesses intrinsic antibiotic resistance mechanisms and commonly exhibits multidrug resistance. Here, we report the evolving resistance profiles of strains isolated from the sputum of a patient being treated for repeated P. aeruginosa infections following cancer resection. Whole genome sequencing of six isolates obtained over a 2-month period revealed two key single nucleotide polymorphisms in the mexR and gyrB genes that affected efflux pump expression and antimicrobial resistance. 相似文献
996.
Retinoic acid controls blood vessel formation by modulating endothelial and mural cell interaction via suppression of Tie2 signaling in vascular progenitor cells 总被引:3,自引:0,他引:3
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Suzuki Y Komi Y Ashino H Yamashita J Inoue J Yoshiki A Eichmann A Amanuma H Kojima S 《Blood》2004,104(1):166-169
Inhibition by all-trans retinoic acid (atRA) of the microvasculature formation in chicken chorioallantoic membrane (CAM) accompanied remarkably reduced numbers of endothelial cells (ECs) and increased numbers of mural cells (MCs) under the chorionic epithelial layer. Ro41-5253 (retinoid antagonist) exerted the opposite effect. Although atRA did not affect the differentiation of murine embryonic stem cell-derived vascular progenitor cells (VPCs) into ECs or MCs, atRA suppressed EC-MC interaction, leading to impaired branching. In both atRA-treated VPC cultures and CAM tissues underneath the chorionic epithelial layer, the expression of angiopoietin-2 (Ang-2; competitor for Ang-1) was enhanced, whereas that of Tie2 (a receptor for Angs) was reduced. Simultaneous treatment with Ang-1 partially blocked RA induction of EC-MC malinteraction and reduction in blood vessel formation. These results suggest that retinoid(s) may reduce EC-MC interaction by down-regulating Tie2 signaling as well as decreased EC numbers, which lead to impaired vascular remodeling. 相似文献
997.
Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma 总被引:14,自引:7,他引:14
Abe M Hiura K Wilde J Moriyama K Hashimoto T Ozaki S Wakatsuki S Kosaka M Kido S Inoue D Matsumoto T 《Blood》2002,100(6):2195-2202
Multiple myeloma (MM) cells cause devastating bone destruction by activating osteoclasts in the bone marrow milieu. However, the mechanism of enhanced bone resorption in patients with myeloma is poorly understood. In the present study, we investigated a role of C-C chemokines, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, in MM cell-induced osteolysis. These chemokines were produced and secreted by a majority of MM cell lines as well as primary MM cells from patients. Secretion of MIP-1alpha and MIP-1beta correlated well with the ability of myeloma cells to enhance osteoclastic bone resorption both in vitro and in vivo as well as in MM patients. In osteoclastogenic cultures of rabbit bone cells, cocultures with myeloma cells as well as addition of myeloma cell-conditioned media enhanced both formation of osteoclastlike cells and resorption pits to an extent comparable to the effect of recombinant MIP-1alpha and MIP-1beta. Importantly, these effects were mostly reversed by neutralizing antibodies against MIP-1alpha and MIP-1beta, or their cognate receptor, CCR5, suggesting critical roles of these chemokines. We also demonstrated that stromal cells express CCR5 and that recombinant MIP-1alpha and MIP-1beta induce expression of receptor activator of nuclear factor-kappaB (RANK) ligand by stromal cells, thereby stimulating osteoclast differentiation of preosteoclastic cells. These results suggest that MIP-1alpha and MIP-1beta may be major osteoclast-activating factors produced by MM cells. 相似文献
998.
Asymptomatic colorectal cancer detected by screening 总被引:2,自引:1,他引:2
Dr. Haruhiko Shida M.D. Kanako Ban M.D. Masao Matsumoto M.D. Kozo Masuda M.D. Tomohiro Imanari M.D. Takehisa Machida M.D. Takashi Yamamoto M.D. Tohru Inoue M.D. 《Diseases of the colon and rectum》1996,39(10):1130-1135
PURPOSE: Colorectal cancer screening has become prevalent. To discuss the efficacy of screening, we studied the characteristics of asymptomatic Colorectal cancer detected by screening. METHODS: This is a retrospective review of patients with colorectal cancer treated at our institution. During the past 20 years, 96 of 1,046 cases of colorectal cancer were asymptomatic and detected by screening. Sixty-one of these cases were detected in the recent five years. The initial screening procedures were fecal occult blood test in 51 cases, sigmoidoscopy or colonoscopy in 18, barium enema in 9, and other tests in 18. RESULTS: Thirteen lesions (14 percent) were smaller than 1.0 cm and 32 (33 percent) were 1–2 cm in size. There were 34 Tis, 21 T1, and 8 T2 tumors. Of the 55 Tis or T1 lesions, 14 showed nonpolypoid growth (5 flat-elevated, 7 flat-elevated with depression, 1 flat, 1 depressed), and 12 of these were detected on endoscopy. Thirty-four cases were TNM Stage 0, 25 were Stage I, 16 were Stage II, 12 were Stage III, and 9 were Stage IV. Sixty-one percent of those detected by screening were in either Stage 0 or Stage I compared with 16 percent in the symptomatic group. Cumulative five-year disease-free survival rates were 100 percent for both Stage 0 and Stage I, 94 percent for Stage II, and 52 percent for Stage III. Overall cumulative five-year survival rate was 87 percent for those detected by screening, compared with 57 percent in symptomatic patients. CONCLUSIONS: Asymptomatic cancers detected by screening were at a less advanced stage. In particular, many nonpolypoid early cancers were detected by endoscopic screening.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995. 相似文献
999.
Kusunoki T Nakahata T Miyanomae T Inoue Y 《American journal of respiratory and critical care medicine》2002,165(4):551-2; author reply 552
1000.
Shimohakamada Y Fukuda N Shinohara K Inoue Y 《[Rinshō ketsueki] The Japanese journal of clinical hematology》2001,42(4):328-331
A 43-year-old man with a 7-year history of low antinuclear factor titer developed Basedow's disease and autoimmune hemolytic anemia (AIHA) simultaneously. Such simultaneous occurrence of these autoimmune disorders has been reported only rarely. Administration of methimazole for Basedow's disease and prednisolone for AIHA was effective for ameliorating both conditions. The patient had the HLA DR2, DRB1 1501 and DPB1 0501 alleles, suggesting a genetic predisposition for these diseases. 相似文献