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Juice Test for Identification of Nonerosive Reflux Disease in Heartburn Patients
Michel R Fernandes,Marina De Oliveira,Sidia M Callegari-Jacques,Gissele V R Gonçalves,Fernando Fornari 대한소화기 기능성질환∙운동학회 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.2
Background/Aims Evaluation of esophageal clearance by orange juice swallowing could be useful to identify different categories of gastroesophageal reflux disease. We determined whether a juice test at the beginning of esophageal pH monitoring can identify nonerosive reflux disease (NERD) among heartburn patients. Methods Multiple swallows of orange juice (pH 3) were performed at the beginning of esophageal pH monitoring in 71 heartburn patients off acid-suppressive therapy. The area between pH drop below 5 and recovery to 5 was calculated from pH tracings and named Delta5 (mmol·L−1·sec). Fifteen healthy subjects served to determine Delta5 cutoff (95th percentile). Patients were classified as NERD, non-NERD (a mix of reflux hypersensitivity, functional heartburn, and undetermined), and erosive disease depending on acid exposure, reflux symptom analysis, and upper endoscopy. Results Delta5 cutoff in healthy subjects was 251 mmol·L−1·sec. Among 71 patients, 23 had NERD, 26 had non-NERD, and 22 had erosive disease. Compared to non-NERD, Delta5 was higher in both NERD (median [interquartile range]: 316 [213–472] vs 165 [105–225]; P < 0.01) and erosive disease (310 [169–625] vs 165 [105–225]; P < 0.01). An elevated Delta5 (> 251 mmol·L−1·sec) showed sensitivity of 74% and specificity of 81% for identification of NERD. Positive and negative likelihood ratios were 3.84 and 0.32 respectively, whereas test accuracy was 78%. Conclusions A juice test with calculation of Delta5 helps in the identification of true NERD among heartburn patients with endoscopy-negative reflux disease. In these patients, an elevated Delta5 could make prolonged reflux testing unnecessary.
Dopaminergic Supersensitivity in G Protein-Coupled Receptor Kinase 6-Deficient Mice
( Raul R. Gainetdinov ),( Laura M. Bohn ),( Tatyana D. Sotnikova ),( Michel Cyr ),( Aki Laakso ),( Alexander D. Macrae ),( Gonzalo E. Torres ),( Kyeong Man Kim ),( Robert J. Lefkowitz ),( Marc G. Caro 전남대학교 약품개발연구소 2003 약품개발연구지 Vol.12 No.-
Phosphatidylethanolamine Enhances Amyloid Fiber-Dependent Membrane Fragmentation
Sciacca, Michele F. M.,Brender, Jeffrey R.,Lee, Dong-Kuk,Ramamoorthy, Ayyalusamy American Chemical Society 2012 Biochemistry Vol.51 No.39
<P>The toxicity of amyloid-forming peptides has been hypothesized to reside in the ability of protein oligomers to interact with and disrupt the cell membrane. Much of the evidence for this hypothesis comes from in vitro experiments using model membranes. However, the accuracy of this approach depends on the ability of the model membrane to accurately mimic the cell membrane. The effect of membrane composition has been overlooked in many studies of amyloid toxicity in model systems. By combining measurements of membrane binding, membrane permeabilization, and fiber formation, we show that lipids with the phosphatidylethanolamine (PE) headgroup strongly modulate the membrane disruption induced by IAPP (islet amyloid polypeptide protein), an amyloidogenic protein involved in type II diabetes. Our results suggest that PE lipids hamper the interaction of prefibrillar IAPP with membranes but enhance the membrane disruption correlated with the growth of fibers on the membrane surface via a detergent-like mechanism. These findings provide insights into the mechanism of membrane disruption induced by IAPP, suggesting a possible role of PE and other amyloids involved in other pathologies.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/2012/bichaw.2012.51.issue-39/bi3009888/production/images/medium/bi-2012-009888_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bi3009888'>ACS Electronic Supporting Info</A></P>
배종석,Michele Ferguson,Rachel Tan,Eneida Mioshi,Neil Simon,James Burrell,Steve Vucic,John R. Hodges,Matthew C Kiernan,Michael Hornberger 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.2
Background and Purpose Tis study investigated the structural and functional changes in the motor system in amyotrophic lateral sclerosis (ALS; n=25) and behavioral-variant frontotemporal dementia (bvFTD; n=17) relative to healthy controls (n=37). Methods Structural changes were examined using a region-of-interest approach, applying voxel-based morphometry for gray-matter changes and difusion tensor imaging for white-matter changes. Functional changes in the motor system were elucidated using threshold-tracking transcranial magnetic stimulation (TMS) measurements of upper motor-neuron excitability. Results The structural analyses showed that in ALS there were more white-matter changes in the corticospinal and motor-cortex regions and more gray-matter changes in the cerebellum in comparison to controls. bvFTD showed substantial gray- and white-matter changes across virtually all motor-system regions compared to controls, although the brainstem was afected less than the other regions. Direct comparisons across patient groups showed that the gray- and white-matter motor-system changes inclusive of the motor cortex were greater in bvFTD than in ALS. By contrast, the functional integrity of the motor system was more adversely afected in ALS than in bvFTD, with both patient groups showing increased excitability of upper motor neurons compared to controls. Conclusions Cross-correlation of structural and functional data further revealed a neural dissociation of diferent motor-system regions and tracts covarying with the TMS excitability across both patient groups. Te structural and functional motor-system integrities appear to be dissociated between ALS and bvFTD, which represents useful information for the diagnosis of motor-system changes in these two disorders.
Two-Step Mechanism of Membrane Disruption by Aβ through Membrane Fragmentation and Pore Formation
Sciacca, Michele F.M.,Kotler, Samuel A.,Brender, Jeffrey R.,Chen, J.,Lee, D.k.,Ramamoorthy, A. Biophysical Society ; Published for the Biophysica 2012 Biophysical journal Vol.103 No.4
Disruption of cell membranes by Aβ is believed to be one of the key components of Aβ toxicity. However, the mechanism by which this occurs is not fully understood. Here, we demonstrate that membrane disruption by Aβ occurs by a two-step process, with the initial formation of ion-selective pores followed by nonspecific fragmentation of the lipid membrane during amyloid fiber formation. Immediately after the addition of freshly dissolved Aβ<SUB>1-40</SUB>, defects form on the membrane that share many of the properties of Aβ channels originally reported from single-channel electrical recording, such as cation selectivity and the ability to be blockaded by zinc. By contrast, subsequent amyloid fiber formation on the surface of the membrane fragments the membrane in a way that is not cation selective and cannot be stopped by zinc ions. Moreover, we observed that the presence of ganglioside enhances both the initial pore formation and the fiber-dependent membrane fragmentation process. Whereas pore formation by freshly dissolved Aβ<SUB>1-40</SUB> is weakly observed in the absence of gangliosides, fiber-dependent membrane fragmentation can only be observed in their presence. These results provide insights into the toxicity of Aβ and may aid in the design of specific compounds to alleviate the neurodegeneration of Alzheimer's disease.
Krumholz, Mark R.,Adamo, Angela,Fumagalli, Michele,Wofford, Aida,Calzetti, Daniela,Lee, Janice C.,Whitmore, Bradley C.,Bright, Stacey N.,Grasha, Kathryn,Gouliermis, Dimitrios A.,Kim, Hwihyun,Nair, Pre IOP Publishing 2015 The Astrophysical journal Vol.812 No.2
<P>We investigate a novel Bayesian analysis method, based on the Stochastically Lighting Up Galaxies (slug) code, to derive the masses, ages, and extinctions of star clusters from integrated light photometry. Unlike many analysis methods, slug correctly accounts for incomplete initial mass function (IMF) sampling, and returns full posterior probability distributions rather than simply probability maxima. We apply our technique to 621 visually confirmed clusters in two nearby galaxies, NGC 628 and NGC 7793, that are part of the Legacy Extragalactic UV Survey (LEGUS). LEGUS provides Hubble Space Telescope photometry in the NUV, U, B, V, and I bands. We analyze the sensitivity of the derived cluster properties to choices of prior probability distribution, evolutionary tracks, IMF, metallicity, treatment of nebular emission, and extinction curve. We find that slug's results for individual clusters are insensitive to most of these choices, but that the posterior probability distributions we derive are often quite broad, and sometimes multi-peaked and quite sensitive to the choice of priors. In contrast, the properties of the cluster population as a whole are relatively robust against all of these choices. We also compare our results from slug to those derived with a conventional non-stochastic fitting code, Yggdrasil. We show that slug's stochastic models are generally a better fit to the observations than the deterministic ones used by Yggdrasil. However, the overall properties of the cluster populations recovered by both codes are qualitatively similar.</P>