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- 검색키워드
- 저자 : FITZGERALD Michael C (검색결과 5 건)
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Vida Bitarafan,Penelope C E Fitzgerald,Tanya J Little,Wolfgang Meyerhof,Tongzhi Wu,Michael Horowitz,Christine Feinle-Bisset 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.3
Background/AimsNutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation)contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shownin cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressedthroughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. Thisstudy aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energyintake. MethodsFourteen healthy, lean men (25 ± 5 years; BMI: 22.5 ± 2.0 kg/m2) received on 4 separate occasions, in randomized, double-blindfashion, 60-minute intraduodenal infusions of quinine hydrochloride at doses totaling 37.5 mg (“Q37.5”), 75 mg (“Q75”) or 225 mg(“Q225”), or control (all 300 mOsmol). Antropyloroduodenal pressures (high-resolution manometry), plasma CCK (radioimmunoassay),and appetite perceptions/gastrointestinal symptoms (visual analog questionnaires) were measured. Ad libitum energy intake(buffet-meal) was quantified immediately post-infusion. Oral quinine taste-thresholds were assessed on a separate occasion using3-alternative forced-choice procedure. ResultsAll participants detected quinine orally (detection-threshold: 0.19 ± 0.07 mmol/L). Intraduodenal quinine did not affect antral, pyloricor duodenal pressures, plasma CCK (pmol/L [peak]; control: 3.6 ± 0.4, Q37.5: 3.6 ± 0.4, Q75: 3.7 ± 0.3, Q225: 3.9 ± 0.4), appetiteperceptions, gastrointestinal symptoms or energy intake (kcal; control: 1088 ± 90, Q37.5: 1057 ± 69, Q75: 1029 ±7 0, Q225: 1077 ± 88). ConclusionQuinine, administered intraduodenally over 60 minutes, even at moderately high doses, but low infusion rates, does not modulateappetite-related gastrointestinal functions or energy intake.
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Searching for Transit Timing Variations and Fitting a New Ephemeris to Transits of TrES-1 b
Paige Yeung,Quinn Perian,Peyton Robertson,Michael Fitzgerald,Martin Fowler,Frank Sienkiewicz,Kalee Tock 한국천문학회 2022 Journal of The Korean Astronomical Society Vol.55 No.4
Based on the light an exoplanet blocks from its host star as it passes in front of it during a transit, the mid-transit time can be determined. Periodic variations in mid-transit times can indicate another planet's gravitational influence. We investigate 83 transits of TrES-1 b as observed from 6-inch telescopes in the MicroObservatory robotic telescope network. The EXOTIC data reduction pipeline is used to process these transits, fit transit models to light curves, and calculate transit midpoints. This paper details the methodology for analyzing transit timing variations (TTVs) and using transit measurements to maintain ephemerides. The application of Lomb-Scargle period analysis for studying the plausibility of TTVs is explained. The analysis of the resultant TTVs from 46 transits from MicroObservatory and 47 transits from archival data in the Exoplanet Transit Database indicated the possible existence of other planets affecting the orbit of TrES-1 and improved the precision of the ephemeris by one order of magnitude. We now estimate the ephemeris to be 2455489.66026 BJD_{TDB} ± 0.00044 d + (3.0300689 ± 0.0000007) d × epoch. This analysis also demonstrates the role of small telescopes in making precise mid-transit time measurements, which can be used to help maintain ephemerides and perform TTV analysis. The maintenance of ephemerides allows for an increased ability to optimize telescope time on large ground-based telescopes and space telescope missions.
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Impact of Cannabis Use on Long-Term Remission in Bipolar I and Schizoaffective Disorder
김성완,Seetal Dodd,Lesley Berk,Jayashri Kulkarni,Anthony de Castella,Paul B. Fitzgerald,김재민,윤진상,MIchael Berk 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.3
ObjectiveaaTo investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders. MethodsaaThe 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months. ResultsaaOf the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group. ConclusionaaCannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders.
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Kwon, Do-Yeon,Lee, Hye Eun,Weitzel, Douglas H.,Park, Kyunghye,Lee, Sun Hee,Lee, Chen-Ting,Stephenson, Tesia N.,Park, Hyeri,Fitzgerald, Michael C.,Chi, Jen-Tsan,Mook Jr., Robert A.,Dewhirst, Mark W.,Le American Chemical Society 2015 Journal of medicinal chemistry Vol.58 No.19
<P/><P>To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and resistance to treatment of most solid tumors, a considerable amount of effort has been made to identify HIF-1 inhibitors for treatment of cancer. Isolated from <I>Saururus cernuus</I>, manassantins A (<B>1</B>) and B (<B>2</B>) are potent inhibitors of HIF-1 activity. To define the structural requirements of manassantins for HIF-1 inhibition, we prepared and evaluated a series of manassantin analogues. Our SAR studies examined key regions of manassantin’s structure in order to understand the impact of these regions on biological activity and to define modifications that can lead to improved performance and drug-like properties. Our efforts identified several manassantin analogues with reduced structural complexity as potential lead compounds for further development. Analogues <B>MA04</B>, <B>MA07</B>, and <B>MA11</B> down-regulated hypoxia-induced expression of the HIF-1α protein and reduced the levels of HIF-1 target genes, including cyclin-dependent kinase 6 (Cdk6) and vascular endothelial growth factor (VEGF). These findings provide an important framework to design potent and selective HIF-1α inhibitors, which is necessary to aid translation of manassantin-derived natural products to the clinic as novel therapeutics for cancers.</P>
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