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Antimutagenic Activity of Berry Extracts
Lyndon L. Larcom,Patricia L. Tate,George Huang,James B. Magee,Kumudini M. Meepagala,David E. Wedge,S. Hope Smith 한국식품영양과학회 2004 Journal of medicinal food Vol.7 No.4
Plants are proven sources of useful anti-tumor and chemopreventative compounds. Hence, identification ofphytochemicals useful in dietary prevention and intervention of cancer is of paramount importance. The initial step in the for-mation of cancer is damage to the genome of a somatic cell producing a mutation in an oncogene or a tumor-suppressor gene.Fresh juices and organic solvent extracts from the fruits of strawberry, blueberry, and raspberry were evaluated for their abil-ity to inhibit the production of mutations by the direct-acting mutagen methyl methanesulfonate and the metabolically acti-vated carcinogen benzo[a]pyrene. Juice from strawberry, blueberry, and raspberry fruit significantly inhibited mutagenesiscaused by both carcinogens. Ethanol extracts from freeze-dried fruits of strawberry cultivars (Sweet Charlie and Carlsbad)and blueberry cultivars (Tifblue and Premier) were also tested. Of these, the hydrolyzable tannin-containing fraction fromSweet Charlie strawberries was most effective at inhibiting mutations.
James A. Smith,Casey J. Jesse,William A. Hanson,Clark L. Scott,David L. Cottle Korean Nuclear Society 2023 Nuclear Engineering and Technology Vol.55 No.6
One of the salient nuclear fuel performance parameters for new fuel types under development is changes in fuel thickness. To test the new commercially fabricated U-10Mo monolithic plate-type fuel, an irradiation experiment was designed that consisted of multiple mini-plate capsules distributed within the Advanced Test Reactor (ATR) core, the mini-plate 1 (MP-1) experiment. Each capsule contains eight mini-plates that were either fueled or "dummy" plates. Fuel thickness changes within a fuel assembly can be characterized by measuring the gaps between the plates ultrasonically. The channel gap probe (CGP) system is designed to measure the gaps between the plates and will provide information that supports qualification of U-10Mo monolithic fuel. This study will discuss the design and the results from the use of a custom-designed CGP system for characterizing the gaps between mini-plates within the MP-1 capsules. To ensure accurate and repeatable data, acceptance and calibration procedures have been developed. Unfortunately, there is no "gold" standard measurement to compare to CGP measurements. An effort was made to use plate thickness obtained from post-irradiation measurements to derive channel gap estimates for comparison with the CGP characterization.
Katie Pricola Fehnel,David L. Penn,Micah Duggins-Warf,Maxwell Gruber,Steven Pineda,Julie Sesen,Alexander Moses-Gardner,Nishali Shah,Jessica Driscoll,David Zurakowski,Darren B. Orbach,Edward R. Smith 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
We investigated (1) EphrinB2 and EphB4 receptor expression in cerebral AVMs, (2) the impact of an altered EphrinB2: EphB4 ratio on brain endothelial cell function and (3) potential translational applications of these data. The following parameters were compared between AVM endothelial cells (AVMECs) and human brain microvascular endothelial cells (HBMVECs): quantified EphrinB2 and EphB4 expression, angiogenic potential, and responses to manipulation of the EphrinB2:EphB4 ratio via pharmacologic stimulation/inhibition. To investigate the clinical relevance of these in vitro data, Ephrin expression was assessed in AVM tissue (by immunohistochemistry) and urine (by ELISA) from pediatric patients with AVM (n=30), other cerebrovascular disease (n=14) and control patients (n=29), and the data were subjected to univariate and multivariate statistical analyses. Compared to HBMVECs, AVMECs demonstrated increased invasion (p=0.04) and migration (p=0.08), impaired tube formation (p=0.06) and increased EphrinB2:EphB4 ratios. Altering the EphrinB2:EphB4 ratio (by increasing EphrinB2 or blocking EphB4) in HBMVECs increased invasion (p=0.03 and p<0.05, respectively). EphrinB2 expression was increased in AVM tissue, which correlated with increased urinary EphrinB2 levels in AVM patients. Using the optimal urinary cutoff value (EphrinB2>25.7pg/μg), AVMs were detected with high accuracy (80% vs. controls) and were distinguished from other cerebrovascular disease (75% accuracy). Posttreatment urinary EphrinB2 levels normalized in an index patient. In summary, AVMECs have an EphrinB2:EphB4 ratio that is increased compared to that of normal HBMVECs. Changing this ratio in HBMVECs induces AVMEC-like behavior. EphrinB2 is clinically relevant, and its levels are increased in AVM tissue and patient urine. This work suggests that dysregulation of the EphrinB2:EphB4 signaling cascade and increases in EphrinB2 may play a role in AVM development, with potential utility as a diagnostic and therapeutic target.
Scaglione, Jamie B.,Akey, David L.,Sullivan, Rachel,Kittendorf, Jeffrey D.,Rath, Christopher M.,Kim, Eung-Soo,Smith, Janet L.,Sherman, David H. WILEY-VCH Verlag 2010 Angewandte Chemie Vol.49 No.33
<B>Graphic Abstract</B> <P>A narrow tunnel: Biochemical and structural analysis of the tautomycetin thioesterase (TE) has provided the first high-resolution structure of a linear-chain-terminating TE in polyketide biosynthesis, showing the enzyme to be stereoselective with a constrained substrate chamber relative to macrolactone-forming thioesterases. <img src='wiley_img_2010/14337851-2010-49-33-ANIE201000032-content.gif' alt='wiley_img_2010/14337851-2010-49-33-ANIE201000032-content'> </P>
Nanopatterned Human iPSC-Based Model of a Dystrophin-Null Cardiomyopathic Phenotype
Macadangdang, Jesse,Guan, Xuan,Smith, Alec S. T.,Lucero, Rachel,Czerniecki, Stefan,Childers, Martin K.,Mack, David L.,Kim, Deok-Ho Springer-Verlag 2015 Cellular and molecular bioengineering Vol.8 No.3
<P>Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer unprecedented opportunities to study inherited heart conditions in vitro, but are phenotypically immature, limiting their ability to effectively model adult-onset diseases. Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the pathogenesis of this disease phenotype is not fully understood. Therefore, we aimed to test whether biomimetic nanotopography could further stratify the disease phenotype of DMD hiPSC-CMs to create more translationally relevant cardiomyocytes for disease modeling applications. We found that anisotropic nanotopography was necessary to distinguish structural differences between normal and DMD hiPSC-CMs, as these differences were masked on conventional flat substrates. DMD hiPSC-CMs exhibited a diminished structural and functional response to the underlying nanotopography compared to normal cardiomyocytes at both the macroscopic and subcellular levels. This blunted response may be due to a lower level of actin cytoskeleton turnover as measured by fluorescence recovery after photobleaching. Taken together these data suggest that DMD hiPSC-CMs are less adaptable to changes in their extracellular environment, and highlight the utility of nanotopographic substrates for effectively stratifying normal and structural cardiac disease phenotypes in vitro.</P>
AMPK Promotes Aberrant PGC1β Expression To Support Human Colon Tumor Cell Survival
Fisher, Kurt W.,Das, Binita,Kim, Hyun Seok,Clymer, Beth K.,Gehring, Drew,Smith, Deandra R.,Costanzo-Garvey, Diane L.,Fernandez, Mario R.,Brattain, Michael G.,Kelly, David L.,MacMillan, John,White, Mic American Society for Microbiology 2015 Molecular and cellular biology Vol.35 No.22
<P>A major goal of cancer research is the identification of tumor-specific vulnerabilities that can be exploited for the development of therapies that are selectively toxic to the tumor. We show here that the transcriptional coactivators peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β) and estrogen-related receptor α (ERRα) are aberrantly expressed in human colon cell lines and tumors. With kinase suppressor of Ras 1 (KSR1) depletion as a reference standard, we used <U>fu</U>nctional <U>si</U>gnature <U>on</U>tology (FUSION) analysis to identify the γ1 subunit of AMP-activated protein kinase (AMPK) as an essential contributor to PGC1β expression and colon tumor cell survival. Subsequent analysis revealed that a subunit composition of AMPK (α2β2γ1) is preferred for colorectal cancer cell survival, at least in part, by stabilizing the tumor-specific expression of PGC1β. In contrast, PGC1β and ERRα are not detectable in nontransformed human colon epithelial cells, and depletion of the AMPKγ1 subunit has no effect on their viability. These data indicate that Ras oncogenesis relies on the aberrant activation of a PGC1β-dependent transcriptional pathway via a specific AMPK isoform.</P>
Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: An Australian Institution’s Experience
Ming Han Lim,Anton R. Lord,Lisa A. Simms,Katherine Hanigan,Aleksandra Edmundson,Matthew J.F.X. Rickard,Russell Stitz,David A. Clark,Graham L. Radford-Smith 대한대장항문학회 2021 Annals of Coloproctolgy Vol.37 No.5
Purpose: We report outcomes and evaluate patient factors and the impact of surgical evolution on outcomes in consecutive ulcerative colitis patients who had restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) at an Australian institution over 26 years.Methods: Data including clinical characteristics, preoperative medical therapy, and surgical outcomes were collected. We divided eligible patients into 3 period arms (period 1, 1990 to 1999; period 2, 2000 to 2009; period 3, 2010 to 2016). Outcomes of interest were IPAA leak and pouch failure.Results: A total of 212 patients were included. Median follow-up was 50 (interquartile range, 17 to 120) months. Rates of early and late complications were 34.9% and 52.0%, respectively. Early complications included wound infection (9.4%), pelvic sepsis (8.0%), and small bowel obstruction (6.6%) while late complications included small bowel obstruction (18.9%), anal stenosis (16.8%), and pouch fistula (13.3%). Overall, IPAA leak rate was 6.1% and pouch failure rate was 4.8%. Eighty-three patients (42.3%) experienced pouchitis. Over time, we observed an increase in patient exposure to thiopurine (P=0.0025), cyclosporin (P=0.0002), and anti-tumor necrosis factor (P<0.00001) coupled with a shift to laparoscopic technique (P<0.00001), stapled IPAA (P<0.00001), J pouch configuration (P<0.00001), a modified 2-stage procedure (P=0.00012), and a decline in defunctioning ileostomy rate at time of IPAA (P=0.00002). Apart from pouchitis, there was no significant difference in surgical and chronic inflammatory pouch outcomes with time.Conclusion: Despite greater patient exposure to immunomodulatory and biologic therapy before surgery coupled with a significant change in surgical techniques, surgical and chronic inflammatory pouch outcome rates have remained stable.