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https://www.readbyqxmd.com/read/28432078/effect-of-4-5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl-carbamoyl-benzoic-acid-am80-on-alveolar-regeneration-in-adiponectin-deficient-mice-showing-a-chronic-obstructive-pulmonary-disease-like-pathophysiology
#1
Hitomi Sakai, Michiko Horiguchi, Tomomi Akita, Chihiro Ozawa, Mai Hirokawa, Yuki Oiso, Harumi Kumagai, Yoshito Takeda, Isao Tachibana, Norikazu Maeda, Chikamasa Yamashita
Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease that causes widespread and irreversible alveolar collapse. Although COPD occurs worldwide, only symptomatic therapy is currently available. The objective of the present study was the development of therapeutic agents to eradicate COPD. Therefore, we focused on 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid (Am80), which is a derivative of all-trans retinoic acid. We evaluated the effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient mice...
April 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28408311/validation-of-a-difficulty-scoring-system-for-laparoscopic-liver-resection-a-multicenter-analysis-by-the-endoscopic-liver-surgery-study-group-in-japan
#2
Shogo Tanaka, Shoji Kubo, Akishige Kanazawa, Yutaka Takeda, Fumitoshi Hirokawa, Hiroyuki Nitta, Takayoshi Nakajima, Takashi Kaizu, Hironori Kaneko, Go Wakabayashi
BACKGROUND: Laparoscopic liver resection (LLR) is widely used for hepatic disease treatment. Preoperative prediction of operative difficulty can be beneficial as a roadmap for surgeons advancing from simple to highly technical LLR. We performed a multicenter analysis to investigate a "difficulty scoring system" for predicting the difficulty of LLR. STUDY DESIGN: The proposed "difficulty scoring system" includes three difficulty levels based on five factors. The system was validated in a cohort of 2,199 patients who underwent LLR at 74 Japanese centers between 2010 and 2014; the difficulty level was rated as low (n = 965), intermediate (n = 891), and high (n = 343)...
April 10, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28404748/components-of-rna-granules-affect-their-localization-and-dynamics-in-neuronal-dendrites
#3
Kazuhiko Mitsumori, Yosuke Takei, Nobutaka Hirokawa
In neurons, RNA transport is important for local protein synthesis. Messenger RNAs (mRNAs) are transported along dendrites as large RNA granules. The localization and dynamics of Puralpha and Stau1, major components of RNA transport granules, were investigated in cultured hippocampal neurons. Puralpha-positive granules were localized in both the shafts and spines of dendrites. In contrast, Stau1-positive granules tended to be localized mainly in dendritic shafts. More than 90% of Puralpha-positive granules were positive for Stau1 in immature dendrites, while only half were positive in mature dendrites...
April 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28401637/alcohol-tolerant-mutants-of-cyanobacterium-synechococcus-elongatus-pcc-7942-obtained-by-single-cell-mutant-screening-system
#4
Sayuri Arai, Kayoko Hayashihara, Yuki Kanamoto, Kazunori Shimizu, Yasutaka Hirokawa, Taizo Hanai, Akio Murakami, Hiroyuki Honda
Enhancement of alcohol tolerance in microorganisms is an important strategy for improving bioalcohol productivity. Although cyanobacteria can be used as a promising biocatalyst to produce various alcohols directly from CO2 , low productivity and low tolerance against alcohols are the main issues to be resolved. Nevertheless, to date, a mutant with increasing alcohol tolerance has rarely been reported.n this study, we attempted to select isopropanol (IPA)-tolerant mutants of Synechococcus elongatus PCC 7942 using UV-C-induced random mutagenesis, followed by enrichment of the tolerant candidates in medium containing 10 g/L IPA and screening of the cells with a high growth rate in the single cell culture system in liquid medium containing 10 g/L IPA...
April 12, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28359889/characterization-of-four-arginine-kinases-in-the-ciliate-paramecium-tetraurelia-investigation-on-the-substrate-inhibition-mechanism
#5
Daichi Yano, Takaya Suzuki, Saki Hirokawa, Kyoko Fuke, Tomohiko Suzuki
The ciliate Paramecium tetraurelia contains four arginine kinase genes (AK1-4). We detected cDNA for only three of the AKs (AK1-3) via PCR. Recombinant AK1-4 were expressed in Escherichia coli and their kinetics parameters determined. AK3 showed typical substrate inhibition toward arginine, and enzymatic activity markedly decreased when arginine concentration increased. This is the first example of substrate inhibition in wild-type phosphagen kinases. To explore the substrate inhibition mechanism, site-directed mutations were generated, targeting the amino acid sequence D-D-S-Q-V at positions 77-81 in P...
March 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28355078/discovery-of-novel-indazole-derivatives-as-orally-available-%C3%AE-3-adrenergic-receptor-agonists-lacking-off-target-based-cardiovascular-side-effects
#6
Yasuhiro Wada, Seiji Nakano, Akifumi Morimoto, Ken-Ichi Kasahara, Takahiko Hayashi, Yoshio Takada, Hiroko Suzuki, Michiko Niwa-Sakai, Shigeki Ohashi, Mutsuhiro Mori, Takatsugu Hirokawa, Satoshi Shuto
We previously discovered that indazole derivative 8 was a highly selective β3-adrenergic receptor (β3-AR) agonist, but it appeared to be metabolically unstable. To improve metabolic stability, further optimization of this scaffold was carried out. We focused on the sulfonamide moiety of this scaffold, which resulted in the discovery of compound 15 as a highly potent β3-AR agonist (EC50 = 18 nM) being inactive to β1-, β2-, and α1A-AR (β1/β3, β2/β3, and α1A/β3 > 556-fold). Compound 15 showed dose-dependent β3-AR-mediated responses in marmoset urinary bladder smooth muscle, had a desirable metabolic stability and pharmacokinetic profile (Cmax and AUC), and did not obviously affect heart rate or mean blood pressure when administered intravenously (3 mg/kg) to anesthetized rats...
April 11, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28341544/echocardiographic-assessment-of-right-ventricular-function-in-routine-practice-which-parameters-are-useful-to-predict-one-year-outcome-in-advanced-heart-failure-patients-with-dilated-cardiomyopathy
#7
Takayuki Kawata, Masao Daimon, Koichi Kimura, Tomoko Nakao, Seitetsu L Lee, Megumi Hirokawa, Tomoko S Kato, Masafumi Watanabe, Yutaka Yatomi, Issei Komuro
BACKGROUND: Right ventricular (RV) function has recently gained attention as a prognostic predictor of outcome even in patients who have left-sided heart failure. Since several conventional echocardiographic parameters of RV systolic function have been proposed, our aim was to determine if any of these parameters (tricuspid annular plane systolic excursion: TAPSE, tissue Doppler derived systolic tricuspid annular motion velocity: S', fractional area change: FAC) are associated with outcome in advanced heart failure patients with dilated cardiomyopathy (DCM)...
March 21, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28337323/structure-based-design-of-ask1-inhibitors-as-potential-agents-for-heart-failure
#8
Marion Lanier, Jason Pickens, Simone V Bigi, Erica L Bradshaw-Pierce, Alison Chambers, Zacharia S Cheruvallath, Derek Cole, Douglas R Dougan, Jacques Ermolieff, Tony Gibson, Petro Halkowycz, Aki Hirokawa, Anthony Ivetac, Joanne Miura, Evan Nunez, Mark Sabat, John Tyhonas, Haixia Wang, Xiaolun Wang, Steve Swann
Apoptosis signal-regulating kinase 1 (ASK1/MAP3K) is a mitogen-activated protein kinase family member shown to contribute to acute ischemia/reperfusion injury. Using structure-based drug design, deconstruction, and reoptimization of a known ASK1 inhibitor, a lead compound was identified. This compound displayed robust MAP3K pathway inhibition and reduction of infarct size in an isolated perfused heart model of cardiac injury.
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28332308/ceacam1-long-isoform-has-opposite-effects-on-the-growth-of-human-mastocytosis-and-medullary-thyroid-carcinoma-cells
#9
Chiyuki Ueshima, Tatsuki R Kataoka, Yusuke Takei, Masahiro Hirata, Akihiko Sugimoto, Mitsuyoshi Hirokawa, Yoshimichi Okayama, Richard S Blumberg, Hironori Haga
Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM1-L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and/or SHP-2. Src family kinases (SFKs) are also known to bind to and phosphorylate CEACAM1-L isoforms. Here, we report that CEACAM1 was uniquely expressed at high levels in both human neoplastic mast cells (mastocytosis) and medullary thyroid carcinoma cell (MTC) lines, when compared with their expression in nonneoplastic mast cells or nonneoplastic C cells...
April 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28325659/construction-of-a-novel-d-lactate-producing-pathway-from-dihydroxyacetone-phosphate-of-the-calvin-cycle-in-cyanobacterium-synechococcus-elongatus-pcc%C3%A2-7942
#10
Yasutaka Hirokawa, Ryota Goto, Yoshitaka Umetani, Taizo Hanai
Using engineered cyanobacteria to produce various chemicals from carbon dioxide is a promising technology for a sustainable future. Lactate is a valuable commodity that can be used for the biodegradable plastic, polylactic acid. Typically, lactate production using engineered cyanobacteria was via the conversion of pyruvate in glycolysis by lactate dehydrogenase. In cyanobacteria, the metabolic flux in the Calvin cycle is higher than that in glycolysis under photoautotrophic conditions. The construction of a novel lactate producing pathway that uses metabolites from the Calvin cycle could potentially increase lactate productivity in cyanobacteria...
March 18, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28269978/differential-diagnosis-between-intraductal-papillary-mucinous-neoplasm-with-an-associated-invasive-carcinoma-and-pancreatic-ductal-adenocarcinoma-on-ultrasonography-the-utility-of-echo-intensity-and-contrast-enhancement
#11
Masato Saito, Naoki Hirokawa, Yoko Usami, Masanori Someya, Koh-Ichi Sakata
Purpose: The aim of this study was to investigate the utility of echo intensity and contrast enhancement in the differential diagnosis between intraductal papillary mucinous neoplasm with an associated invasive carcinoma (IPMN-IC) and pancreatic ductal adenocarcinoma (PDAC) on ultrasonography. Methods: This study included eight and 33 patients who had pathologically confirmed IPMN-IC and PDAC, respectively, and were enrolled for a comparative analysis of the sonographic features of the tumors...
February 4, 2017: Ultrasonography
https://www.readbyqxmd.com/read/28246648/minute-hyalinizing-trabecular-tumor-misinterpreted-as-a-blood-vessel-on-ultrasonography-a-case-report
#12
Kumiko Tajiri, Mitsuyoshi Hirokawa, Maki Oshita, Hisashi Ota, Ayana Suzuki, Kaoru Kobayashi, Hirotoshi Nakamura, Akira Miyauchi
No abstract text is available yet for this article.
February 2017: Ultrasound International Open
https://www.readbyqxmd.com/read/28228269/diverse-central-projection-patterns-of-retinal-ganglion-cells
#13
Emily M Martersteck, Karla E Hirokawa, Mariah Evarts, Amy Bernard, Xin Duan, Yang Li, Lydia Ng, Seung W Oh, Benjamin Ouellette, Joshua J Royall, Michelle Stoecklin, Quanxin Wang, Hongkui Zeng, Joshua R Sanes, Julie A Harris
Understanding how >30 types of retinal ganglion cells (RGCs) in the mouse retina each contribute to visual processing in the brain will require more tools that label and manipulate specific RGCs. We screened and analyzed retinal expression of Cre recombinase using 88 transgenic driver lines. In many lines, Cre was expressed in multiple RGC types and retinal cell classes, but several exhibited more selective expression. We comprehensively mapped central projections from RGCs labeled in 26 Cre lines using viral tracers, high-throughput imaging, and a data processing pipeline...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28183081/management-of-abdominal-drainage-after-hepatic-resection
#14
Yoshihiro Inoue, Yoshiro Imai, Nao Kawaguchi, Fumitoshi Hirokawa, Michihiro Hayashi, Kazuhisa Uchiyama
BACKGROUND: Routine drainage after partial hepatic resection has long been controversial. METHODS: Three hundred and twenty-eight patients who underwent hepatic resections for liver tumors without biliary-enteric and gastrointestinal anastomoses were analyzed using propensity score matching analysis with respect to if and when a prophylactic drain was used and for how long. The criteria for drain placement were established and validated. RESULTS: Our criteria for drain placement were chosen according to postoperative percutaneous abdominal drainage risk factors, organ/space surgical site infections (SSIs), hepatic resection method, intraoperative bile leakage and operative time (≥300 min)...
February 10, 2017: Digestive Surgery
https://www.readbyqxmd.com/read/28178316/md-simulation-of-the-tat-cyclin-t1-cdk9-complex-revealing-the-hidden-catalytic-cavity-within-the-cdk9-molecule-upon-tat-binding
#15
Kaori Asamitsu, Takatsugu Hirokawa, Takashi Okamoto
In this study, we applied molecular dynamics (MD) simulation to analyze the dynamic behavior of the Tat/CycT1/CDK9 tri-molecular complex and revealed the structural changes of P-TEFb upon Tat binding. We found that Tat could deliberately change the local flexibility of CycT1. Although the structural coordinates of the H1 and H2 helices did not substantially change, H1', H2', and H3' exhibited significant changes en masse. Consequently, the CycT1 residues involved in Tat binding, namely Tat-recognition residues (TRRs), lost their flexibility with the addition of Tat to P-TEFb...
2017: PloS One
https://www.readbyqxmd.com/read/28176151/frequent-braf-v600e-and-absence-of-tert-promoter-mutations-characterize-sporadic-pediatric-papillary-thyroid-carcinomas-in-japan
#16
Naoki Oishi, Tetsuo Kondo, Tadao Nakazawa, Kunio Mochizuki, Tomohiro Inoue, Kazunari Kasai, Ippei Tahara, Tomonori Yabuta, Mitsuyoshi Hirokawa, Akira Miyauchi, Ryohei Katoh
Pediatric papillary thyroid carcinoma (PTC) has unique features but requires further genetic investigation. Moreover, there has been increasing concern about the risk for pediatric PTC in Japan after the Fukushima accident. This study aims to evaluate the frequencies of BRAF and TERT promoter mutations and to examine their significance in non-radiation-associated pediatric PTCs in Japan. We enrolled 81 pediatric PTC patients aged ≤20 years. The control group included 91 adult PTCs from patients >20 years old...
February 7, 2017: Endocrine Pathology
https://www.readbyqxmd.com/read/28150740/tert-promoter-mutations-and-ki-67-labeling-index-as-a-prognostic-marker-of-papillary-thyroid-carcinomas-combination-of-two-independent-factors
#17
Michiko Matsuse, Tomonori Yabuta, Vladimir Saenko, Mitsuyoshi Hirokawa, Eijun Nishihara, Keiji Suzuki, Shunichi Yamashita, Akira Miyauchi, Norisato Mitsutake
Although most papillary thyroid carcinomas (PTCs) have a good prognosis, a small but certain fraction shows aggressive behavior. Therefore, a novel and well-performing molecular marker is needed. In the present study, we assessed the impact of the combination of the TERT promoter/BRAF mutations and Ki-67 labeling index (LI) as a prognostic marker in PTC patients. Of 400 PTC samples, 354 were successfully genotyped for both TERT promoter/BRAF and analyzed for Ki-67 LI. Based on the combination of the mutational status and Ki-67 LI, the cases were categorized into three groups: high-, middle-, and low-risk...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28112749/reduced-intensity-conditioning-allogeneic-hematopoietic-cell-transplantation-for-younger-patients-with-acute-myeloid-leukemia-a-registry-based-study
#18
M Yanada, S Kurosawa, T Kobayashi, Y Ozawa, H Kanamori, N Kobayashi, M Sawa, H Nakamae, N Uchida, H Hashimoto, T Fukuda, M Hirokawa, Y Atsuta, S Yano
Clinical efficacy of allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) for younger patients remains unclear. We therefore performed a retrospective registry-based study to evaluate outcomes for patients with AML aged between 16 and 49 years who underwent RIC allogeneic HCT. Patients receiving RIC (N=125) showed significantly worse survival than those receiving myeloablative conditioning (MAC; N=1,554) (47.7% for RIC and 54.2% for MAC at 4 years, P=0.047). However, the difference became marginal after adjustment for patient characteristics (P=0...
January 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28097410/intercostal-trocars-enable-easier-laparoscopic-resection-of-liver-tumors-in-segments-7-and-8
#19
Fumitoshi Hirokawa, Michihiro Hayashi, Mitsuhiro Asakuma, Tetsunosuke Shimizu, Yoshihiro Inoue, Kazuhisa Uchiyama
BACKGROUND: Laparoscopic resection of posterosuperior (PS) tumors of the liver is more difficult than that of anterolateral (AL) tumors, owing to the narrow surgical field in the PS location. In this retrospective cohort study, our aim was to determine if port insertion through the intercostal space would lead to improved outcomes for laparoscopic resection of tumors in PS liver segments 7 and 8. METHOD: Between January 2006 and December 2015, 153 patients underwent laparoscopic resection of solitary liver tumors at Osaka Medical College Hospital...
January 17, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28090072/reconsideration-of-inferior-vena-cava-parameters-for-estimating-right-atrial-pressure-in-an-east-asian-population%C3%A3-comparative-simultaneous-ultrasound-catheterization-study
#20
MULTICENTER STUDY
Takayuki Kawata, Masao Daimon, Seitetsu L Lee, Koichi Kimura, Naoko Sawada, Shuo-Ju Chiang, Keitaro Mahara, Takeshi Okubo, Tomoko Nakao, Megumi Hirokawa, Boqing Xu, Tomoko S Kato, Masafumi Watanabe, Yutaka Yatomi, Issei Komuro
BACKGROUND: Ultrasound measurements of the inferior vena cava (IVC) diameter (IVCD), together with its respiratory variation, provide a noninvasive estimate of right atrial pressure (RAP). However, there is a paucity of studies that have compared this technique with simultaneous catheterization. We explored the best cut-off values of IVC parameters for elevated RAP in comparison with RAP measured by catheterization.Methods and Results:We prospectively enrolled 120 East Asian patients who were scheduled for catheterization...
February 24, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
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