tbuckley/cabot-search huggingface dataset:
Abstract 17095: Caveolin-1 Mediates Cellular Protective Effects of a High-Molecular Weight Polyethylene Glycol-Based Copolymer, PEG 15-20 During Hypoxia-Reoxygenation in Cardiac Myocytes
Authors: Ricky Malhotra, Tiju Theccanat, Shahab A Akhter
Journal: Circulation (2011)

Ischemic heart disease is the primary etiology for the development of heart failure. We recently demonstrated that PEG 15-20 protects cardiac myocytes from hypoxia-reoxygenatiion (H-R)-induced cell death and preserves ventricular function. In the present study we investigated our hypothesis that PEG 15-20 exerts its beneficial effect by stabilizing sarcolemmal lipid rafts particularly by its effect on Caveolin-1 (Cav-1). Cav-1 alongwith Cav-3, the principal structural components of caveolar domains are abundantly expressed in the myocardium and implicated in the pathogenesis of ischemic injury. Cardiac myocytes were exposed to 30 minutes of hypoxia (2% O 2 , 5% CO 2 , 93% N 2 ) followed by 3 hours of reoxygenation (5% CO 2 , 95% air) with cells treated with 5% PEG 15-20 during reoxygenation. Adenoviral-mediated knockdown of Cav-1 in cardiac myocytes by RNA interference reversed the anti-apoptotic effect of PEG 15-20 both in terms of caspase 3 activity (6.7±1.2 vs. 3.8±0.76 fluorometric units/mg protein) and TUNEL staining (38±7 vs. 17±3 apoptotic cells). Cav-1 knockdown also abrogated the decrease in oxidative stress mediated by PEG 15-20 during H-R as measured by superoxide radical generation (4.3±0.65 vs. 1.4±0.32 nmoles/min/mg protein with PEG 15-20 alone). Further Cav-1 knockdown mitigated the increased pro-survival phosphorylation of Akt, GSK-3β and ERK1/2 observed with PEG15-20 during H-R. Importantly maintenance of cardiac myocyte β-adrenergic signaling that is critical for myocardial function that was observed with PEG 15-20 treatment during H-R in cardiac myocytes was also reversed with knockdown of Cav-1(16±1.8 vs. 28±2.6 pmol cAMP/mL with PEG 15-20 alone). Finally, confocal microscopy revealed that PEG 15-20 mediated preservation of sarcolemmal lipid-raft architecture during H-R was abolished in cells deficient in Cav-1as seen by increased lipid raft coalescence. These studies demonstrate that PEG 15-20 primarily exerts its cardiac-specific pro-survival and anti-apoptotic effects during H-R by binding and stabilizing Cav-1 in the caveolar domains. Therapeutic strategies to augment maintenance of lipid raft micro architecture in the cardiac sarcolemmal membrane may improve survival after ischemic injuries.
Elimination of alcohol from blood varies
Authors: Janusz, Knepil, 夏志伟（译）
Journal: BMJ (2005)

Paton认为（原文见本刊2005年第3期176页）：血液中酒精的清除总是与时间呈线性关系，即符合零级动力学1。他也提到了清除过程是由酶促反应介导的。但在大多数情况下，酶的活性的变化符合一级动力学，除非限速反应已达“饱和”状态。
Treatment of osteoporosis is not futile
Authors: David B Lee, Robert A Adler, Robert F Gagel
Journal: BMJ (2015)

We agree with the authors that osteoporosis and osteoporotic fractures are a problem worldwide, but we disagree with the premise that the treatment of osteoporosis is futile.1 The National Bone Health Alliance and its partners are focused on identifying and treating people who have had an osteoporotic fracture and are at high …
Abstract 18666: What are Key Factors to Achieve Better Stent Apposition at Left Main Bifurcation by Culottes Stenting Technique? Micro-CT Analysis Using Bifurcated Elastic Coronary Artery Models
Authors: Yutaka Hikichi, Takafumi Ohba, Tsuyoshi Inukai, Sho Kishigami, Jun Arai, Mitsuo Umezu, Koichi Node, Kiyotaka Iwasaki
Journal: Circulation (2014)

Introduction: We hypothesize that restenosis or stent thrombosis at left main (LM) bifurcation after two-stenting are caused by incomplete stent apposition to coronary artery which may be affected by bifurcation angles, stent design, stent size, and stenting techniques. We investigated influences of those factors on stent apposition using bifurcated elastic coronary artery models (CAMs) to understand better two-stenting with culottes technique. Methods: Based on CT angiography of 209 patients, three LM bifurcated CAMs were manufactured. Focusing on magnitude of the angles between LMT and LCx, the angle data were divided into three groups. Each average model such as the LMT-LCx, LAD-LCx, and LMT-LAD angles of 143°, 59.1°, and 144.3° (mild model: MiM), 121.9°, 70.6°, and 141.4° (moderate model: MoM), and 99.1°, 86.2°, and 143.6° (severe model: SM) was manufactured. Each model has 60% stenosis along with LMT to LAD, and 50% stenosis at LCx ostium. Diameters of LMT, LAD, and LCx were 4.5mm, 3.5mm, and 3.0mm. Two-link Nobori (N) and 3-link Xience V (X) stent were employed for comparison. Moreover, differences in selection of 3.5mm-diameter (3.5D) or 3.0D stent for LCx on stent apposition were investigated, because stent expansion capability differs between the two sizes. When 3.5D stents were used for LCx, stents were deployed at balloon inflation pressure of 4atm for N and 5 or 6atm for X, respectively. Then, additional stent expansion with a 3D balloon was performed. Culottes stenting and final kissing balloon inflation were performed by a single doctor. Stent incomplete apposition volume (SIAV) was quantitatively assessed using micro-CT. Results: When 3D stents were used for LCx, there were no differences in SIAV among MiM, MoM, and SM, both for N and X. Interestingly, when 3.5D stents were used for LCx, SIAV of N were smaller in SM than that in MiM and MoM, respectively (p&lt;0.05), and SIAV of X in SM were larger than that in MiM (p&lt;0.05). When 3D stents were used for LCx, SIAV were comparable between N and X, regardless of the bifurcation angles. When 3.5D stents were used for LCx, SIAV of N were smaller than that of X in MoM and SM (p&lt;0.05). Conclusions: The bifurcation angle between LMT and LCx, stent design, and stent size for LCx were key factors to reduce SIAV in culottes stenting.
Asthma clusters in a real asthmatic population, treated in secondary medical care
Authors: Cláudia Chaves Loureiro, Pedro Sá Couto, Ana Todo-Bom
Journal: European Respiratory Journal (2014)

Background: Due to asthma heterogeneity new analyses strategies were developed in order to group patients, namely by cluster approach, leading to the emergency of new endotypes distinguished by the extension of Th2 response. Our study intended to cluster a real asthmatic population, treated in secondary medical care, including severe asthmatic patients, to better understand the underlying mechanism of this disease.

Methods: Patients with asthma were recruited from outpatient clinic. SPSS ® Software, version 20.0 (SPSS, Inc., Chicago, IL) was used for cluster and inferential analyses, in a non-supervised way. Chosen variables included demographic data; comorbidities; disease control, quality of life and risk assessment; lung function; blood biomarkers.

Results : 57 elements were included and distributed in 5 clusters (C). C1 (n=7): more severe patients with late asthma onset, fixed airway obstruction, being frequent smoke exposure and AINE´s hypersensitivity; C2 (n=19): obese female asthmatics, highly symptomatic with late disease onset; C3 (n=10): brittle asthma phenotype, in young allergic females with early disease onset; C4 (n=15): older females with moderate allergic asthma and long disease evolution; C 5 (n=6): eosinophilic mild allergic asthma, early disease onset.

Conclusions : Distribution was set in 5 clusters, overlapping with findings from other studies. Adapting our results to known plausable endotypes, C5 can be associated with Th2 response; C2 with non-Th2 response; C1 and C4 with mixed response (the first conditioned by smoke exposure and AINE´s hypersensitivity and the second by weight gain). Finally, C3 might be associated with mixed response, with Th2 prevalence.
Abstract 16146: Renin-Angiotensin Axis Blockade Attenuates Abdominal Aortic Expansion in Humans
Authors: Daniel Silverberg, Anan Younis, Dmitry Yakubovitch, Rony Reinitz, Basheer S yousif, Moshe Halak, Ehud Grossman, Jacob Schneiderman
Journal: Circulation (2013)

Introduction: The renin-angiotensin system (RAS) has been implicated in abdominal aortic aneurysm (AAA) development in mice and in humans. Angiotensin II (Ang II) signaling was suggested to promote...
Abstract 9386: ASK2 is a Novel Factor Associated with Salt-Sensitive Hypertension
Authors: Keiichiro Kataoka, Nobutaka Koibuchi, Kensuke Toyama, Daisuke Sueta, Yi-Fei Dong, Hisao Ogawa, Shokei Kim-Mitsuyama
Journal: Circulation (2011)

Background: Apoptosis signal-regulating kinase(ASK)1 and ASK2 are MAP3Ks activated by oxidative stress. We have shown that ASK1 has a pivotal role in cardiovascular diseases. ASK2 has been identified as a binding protein for ASK1, and both ASK1 and ASK2 control their respective activities. Cardiovascular phenotypes of ASK2 deficient mice (ASK2KO) have not been reported. Methods and Results: We confirmed ASK2 mRNA expression in hearts, aortas, and kidneys utilizing in situ hybridization . ASK2KO had different phenotypes from ASK1 deficient mice (ASK1KO); ASK2KO have hypertension with significant cardiac hypertrophy and fibrosis. To further characterize the hypertension of ASK2KO, we implanted telemetry units in mice to monitor 24 h variability of blood pressure (BP) and heart rates. ASK2KO had a circadian rhythm in BP, and the differences in systolic BP between ASK2KO and WT was greater in dark periods than in light periods. There were no differences in locomotor activities or heart rates between ASK2KO and WT. There were no significant differences between ASK2KO and WT in sympathetic nerve activities or in parameters pertaining to the renin-angiotensin system. The ratio of ASK2KO urine Na/K in dark was lower than that in WT, and urine Ca excretion in ASK2KO was greater than in WT, suggesting that ASK2KO have renal tubular dysfunctions. We fed a high-salt diet to ASK2KO to examine salt sensitivity. Telemetry analysis revealed that blood pressure of ASK2KO was increased by high-salt diets; furthermore, high salt diets-induced BP differences between ASK2KO and WT were greater in dark than in light. High salt-induced urine Ca excretion levels were significantly greater in ASK2KO than in WT. Heart weights of ASK2KO were higher than those of WT at 8 days after a high-salt diet. ASK2KO therefore have salt sensitive hypertension with cardiac hypertrophy, and there are significant differences in renal excretion levels of electrolytes between ASK2KO and WT. Hypertension of ASK2KO does not depend upon the presence of ASK1 because ASK2 and ASK1 double deficient mice also have hypertension. Conclusion: ASK2 is a novel factor that is involved in the pathogenesis of salt-sensitive hypertension.
Study on the relationship of taxol-resistance of ovarian carcinoma with the amplification of 2p22 on chromosome and the expression of hmsh2 gene
Authors: Hongxia Li
Journal: Cancer Research (2006)

1258   Objective To investigate the difference of DNA copy number and gene expression on chromosome and their correlation with taxol-resistance of ovarian carcinoma. Methods Comparative genomic hybridization was performed on the taxol-resistant cell lines of OC3/Tax300, OC3/Tax50, and their parent cell OC3. The hmsh2 gene which located in the 2p22 of amplification area on chromosome was screened out .The expression of hmsh2 gene was examined in all three cell lines, 33 cases of ovarian cancers who received taxol based chemotherapy previously(group1), and 21 cases of ovarian cancer who never received chemotherapy before operation(group2)by reverse transcription-polymerase chain reaction(RT-PCR). Results gains of 2pter-p21, 3q, 5p, and 9 were detected in all three cell lines. Gain of 10 was only observed in OC3. Losses of chromosomes 1, 4, and 6 were detected in all three cell lines. Loss of 3p was detected in OC3 and OC3/Tax300. Losses of 7q and 8p were only observed in OC3. Amplification (high-copy-number gain) of 10q22 was observed in OC3 and OC3/Tax50. The most interesting finding was that amplification of 2p22 was only detected in OC3/Tax300.Over-expression of hmsh2 gene in OC3/Tax300 and weak- expression in OC3/Tax50 were detected but not in OC3 cell. The expression rates in group1 and group2 were 93.9%(31/33)and 47.6%(10/21)respectively, p=0.0001. The expression rates in serous,mucous and endometrium cancers were 76.9%(20/26), 66.7%(14/21)and 42.9%(3/7)respectively. There were no significant difference among them. The expression rate in low differential cancer was 93.3% ,higher than that of 54.2% in moderate and good differential cancers significantly, p=0.0008. Conclusion Amplification of 2p22 on chromosome and over-expression of hmsh2 gene may be associated with taxol-resistance of ovarian carcinoma. Keywords ovarian carcinoma; taxol-resistant cell lines; CGH; hmsh2 gene
Potentiation of chemotherapeutics on gliomas by IL13 receptor targeted liposomes
Authors: Achuthamangalam B. Madhankumar, Nodar Suruguledze, Becky Slagle-Webb, Jonas M. Sheehan, James R. Connor
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3077 

The toxic side effects and poor response rates associated with many of the cancer drugs used to treat brain tumors underline the demand for an improvement in current chemotherapeutic protocols for glioma therapy. One approach for improving drug delivery and uptake by tumor cells is to use targeted nanovesicles. IL13Rα2, a receptor for interleukin-13 (IL13), is restrictively expressed in high-grade astrocytomas. Previously, we demonstrated the selective targeting ability of IL13 conjugated liposomes to high grade astrocytomas and the ability of these liposomes to cross the blood brain barrier. In this study we test the hypothesis that IL13 conjugated liposomes can be used to deliver cytotoxins or siRNA to tumor cells effectively. The liposomes ranged in size from 50-150 nm and encapsulated doxorubicin(DXR), BCNU, or siRNA for the H-subunit of ferritin. The latter was chosen because H-ferritin has been found in the nuclei of cancer cells. Various glioma cells were exposed to DXR or BCNU for 24 or 48h with or without transfecting them with siRNA. The effects of the liposomes encapsulating pharmaceutical agents were compared against unencapsulated cytotoxins or non-targeted liposomal cytotoxins. We could observe higher DXR accumulation in glioma cells when they are treated with liposomes conjugated with IL13 using both direct fluorescence microscopy and flow cytometry. Increased uptake of DXR by glioma cells implies decreased efflux mediated by Pgp, which is the major determinant of multidrug resistance (MDR). We could also observe an enhanced cytotoxicity of IL13 conjugated liposomal drug on glioma cells when compared to unconjugated liposomal drug. Transfecting U251 cells with the siRNA for H-ferritin increased the vulnerability of cells to DXR and BCNU and radiation. The siRNA for H-ferritin could be encapsulated into the IL13 conjugated nanovesicles and delivered to the glioma cells. The siRNA was functional as demonstrated by the decrease in H-ferritin and the increase in vulnerability to chemotherapeutics. These results show the efficacy of a novel selective targeting delivery system for tumor cells and a promising new mechanism involving siRNA for H-ferritin. In vivo studies are in progress.
Effect of previous trauma on acute plasma cortisol level following rape
Authors: H S Resnick, R Yehuda, R K Pitman, D W Foy
Journal: American Journal of Psychiatry (1995)

The authors examined the relationships among history of previous assault, severity of rape, acute plasma cortisol level after rape, and development of rape-related post-traumatic stress disorder (PTSD).Blood samples were drawn from 37 adult female rape victims within 51 hours after they had been raped. The subjects were assessed for history of previous assault and for the presence of PTSD 17-157 days (mean = 90 days) after the rape.Women with a history of previous assault had a lower mean acute cortisol level after the rape but a higher probability of subsequently developing PTSD. A significant interaction between history of previous assault and the severity of the index rape was observed: only women who had never been assaulted before had higher cortisol levels following high-severity rapes (those which included injury or multiple types of penetration) than low-severity rapes.The authors conclude that previous traumatization may attenuate the acute cortisol response to trauma.
Abstract 2545: Elimination of Pulmonary Vein Firing and Fractionated Atrial Potentials by Ablation of Autonomic Ganglionated Plexi
Authors: Hiroshi Nakagawa, Gal Hayam, Benjamin J Scherlag, Atsushi Ikeda, Ralph Lazzara, Warren M Jackman
Journal: Circulation (2009)

Recent animal studies show that ganglionated plexi (GP) stimulation produces pulmonary vein firing (PV) and fractionated atrial potentials (FAP) by shortening refractoriness of PV/atrial myocardium...
The homeodomain protein Six1 regulates Ezrin gene transcription through recruitment of the CREB-binding protein.
Authors: Yanlin Yu, Pingyao Zeng, Shelley L. Berger, Glenn Merlino
Journal: Cancer Research (2006)

5141   Ezrin is a member of the ERM family (Ezrin-Radixin-Moesin) and serves as a physical and functional linker between the plasma membrane and the actin cytoskeleton. By organizing membrane-cytoskeleton - associated complexes, Ezrin mediates cellular activities such as survival, adhesion, migration and invasiveness, thereby influencing tumor development and progression. Ezrin expression is enhanced in metastases of mammary and pancreatic adenocarcinoma, osteosarcoma and melanoma. Previously, we identified Ezrin as a critical regulator of metastasis in a mouse model of the pediatric cancer rhabdomyosarcoma (Yu, et al., Nature Medicine, 2004). Although many studies highlight the important role of Ezrin in tumorigenesis, little is known about the regulation of Ezrin expression. We have found that Six1, a homeodomain-containing transcription factor required for skeletal muscle development, can bind to the Ezrin gene (VIL2) promoter and regulate its transcription. Recently, we discovered that epigenetic covalent modifications to histones within nucleosomes of the Ezrin gene promoter are linked to Ezrin expression. Moreover, Six1 regulates Ezrin gene transcription through recruitment of the CREB-binding protein (CBP).
Abstract 15260: Prodromal Symptoms for Acute Coronary Syndrome in Men and Women
Authors: Nadia Khan, Stella Daskalopoulou, Meytal Avgil, Colleen Norris, Igor Karp, Roxanne Pelletier, Louise Pilote, Genesis Praxy Investigators
Journal: Circulation (2013)

Introduction: Prodromal symptoms occur prior to acute coronary syndrome (ACS) and may provide an opportunity for early intervention. We determined the frequency of prodromal symptoms, treatment see...
AIR POLLUTION: The Oxidative Punch of Wildfires
Authors: Carol Potera
Journal: Environmental Health Perspectives (2009)

The Oxidative Punch of Wildfires Thick smoke routinely cloaks Southern California hills, highways, and neighborhoods during this region's autumn wildfire season, with drought contributing to worse fires than usual in the past two years.Wildfire emissions generate larger aerosols than those produced by vehicles-up to 0.4 micrometers (µm) in diameter compared with less than 0.15 µm-according to a new study led by Constantinos Sioutas, a professor of civil and environmental engineering at the University of Southern California, Los Angeles.In findings published online 6 January 2009 ahead of print in Environmental Science & Technology, the larger particles emitted by fires activated a standard assay of oxidative stress even more potently than traffic pollutants.The performance of different types of particulate matter in oxidative stress tests may provide clues as to how these pollutants cause damage such as proinflammatory or cytotoxic effects.Sioutas and colleagues took advantage of wildfires burning in Southern California in October 2007 to investigate their impact on urban air quality relative to traffic pollutants, with a special emphasis on particulate matter small than 2.5 µm in diameter (PM 2.5 ).The researchers collected air samples on the University of Southern California campus, within 150 meters of a busy freeway near downtown Los Angeles.A series of wildfires had started on 20 October 2007, burning more than 500,000 acres of land and stretching from Santa Barbara County to the Mexican border.When air samples were collected on October 24, 25, and 27, fires were raging within 20 miles of the collection site.Measurements were taken from 4:30 p.m. until 10:30 a.m. the following day to capture pollution from evening and morning rush hour traffic as well as from the fires themselves.The fires in Los Angeles County were under control by October 30; post-fire samples collected on November 1 and 14 represented mostly traffic emissions.Compared with postfire samples, samples collected on the three fire days in October contained a higher number of particles larger than 0.1 µm in diameter.Both carbon monoxide and nitrogen monoxide levels increased by threefold during fire days, while levels of other air pollutantsozone, nitrogen dioxide, most polycyclic aromatic hydro carbons, iron, copper, chromium, zinc, nickel, and vanadium-remained the same.In addition, during the fire period there was an approximate doubling in several indicators for biomass burning: levoglucosan, water-soluble organic carbon, and various minerals (magnesium, phosphorus, potassium, and manganese).Various chemical components of PM 2.5 fuel oxidative stress and are toxic
Abstract 14198: Pre-Conditioning of Stem Cell With Celastrol to Enhance Their Therapeutical Potential
Authors: Shant Der Sarkissian, Melanie Borie, Pavel Hamet, Nicolas Noiseux
Journal: Circulation (2011)

Background: Stem cell transplantation is a potential approach to repopulate the injured myocardium and restore function. Cellular therapy is limited by several issues including cell scarcity, survi...
Abstract 9480: Persistent MR Reduction With Stabilization of LV Remodeling and Following Chronic Polymer-Mesh Device on Infarcted Myocardium in a Chronic Ischemic MR Model
Authors: Akihisa Kataoka, Xin Zeng, Michael Garcia, Margo Seybolt, Suzanne Sullivan, J. Luis Guerrero, Maryanne Muriuki, Adam Kozak, Gavin Braithwaite, Mark D Handschumacher, Robert A Levine, Judy Hung
Journal: Circulation (2014)

Background: Mitral valve repair with ring annuloplasty for ischemic mitral regurgitation (IMR) is associated with significant recurrent IMR due to continued left ventricular (LV) remodeling as it does not directly address LV and mitral valve tethering. We aimed to assess chronic implantation of novel polymer based mesh device to reduce IMR reduction and reverse LV remodeling. Methods: Five Dorset sheep underwent ligation of second and third circumflex obtuse marginal branches to produce chronic IMR after 8 weeks. Poly-mesh was attached to the infarcted myocardium underlying the papillary muscle with a further 8 weeks follow-up. In addition, chronic IMR was produced in 5 untreated control sheep. IMR severity was assessed by 2D vena contracta width (VCW) and 3D vena contracta area (VCA). LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) by 2D echo and hemodynamic data were also obtained at each baseline, chronic MR, and chronic poly-mesh stages. Results: In all sheep, after poly-mesh attachment, IMR decreased and this reduction persisted over 8 weeks (VCW 0.42±0.09 to 0.08±0.12cm; VCA 0.13±0.08 to 0.05±0.08cmsq, p&lt;0.01) with significant increase in Emax (1.1±0.5 to 2.9±0.7mmHg/ml, p&lt;0.05). There were no significant changes in LVEF (45.4±6.7 vs 42.6±3.5%, p=NS). Importantly, LV EDV and ESV at chronic poly-mesh stage were reduced compared to the chronic MR stage (EDV 110±15 to 88±18ml, p&lt;0.05; ESV 61±14 to 51±12ml, p=NS) and % increases of both EDV and ESV from chronic MR to chronic poly-mesh stage were significantly lower than those of untreated control sheep (%EDV change -22±11 vs 11±10%, p&lt;0.01; %ESV change -10±14 vs 9±10%, p&lt;0.05) (FIGURE). Conclusions: Chronic follow up after polymer-mesh device attachment shows the stabilization of mitral-LV complex in a chronic IMR model, causing persistent reduction of IMR and preventing continued LV remodeling.