tbuckley/cabot-search huggingface dataset:
Abstract P101: Genetic Variation of Phenylethanolamine-N-methyltransferase Influences Cardiovascular Function in Healthy Humans
Authors: Abdulaziz A Mohammed, Courtney M Wheatley, Nicholas A Cassuto, Eric M Snyder
Journal: Circulation Research (2011)

Objectives: Genetic susceptibility to hypertension can be caused by alterations in cardiovascular and/or renal function. Previous work using genome-wide association studies have demonstrated that the gene that encodes phenylethanolamine-N-methyltransferase (PNMT) is a candidate for hypertension. Follow-up studies confirmed that the gene that encodes PNMT may alter susceptibility to hypertension in African Americans, although no mechanistic data was assessed. Genetic variation of PNMT alters the catecholamine response to exercise, and variation of PNMT at position -182 has been associated with susceptibility to multiple sclerosis. Methods: We sought to determine the influence of genetic variation of PNMT (A-182G) on renal Na + handling and cardiovascular function in humans. We collected serum epinephrine (Epi) and norepinephrine (NE), 24-hour urine, serum Na + , K + , and creatinine, and measured cardiac output (Q, acetylene rebreathing), heart rate (HR, 12-lead EKG), blood pressure (systolic, SBP, diastolic, DBP, and calculated mean arterial, MAP) and calculated fractional excretion of Na + (F E Na), stroke volume (SV), and systemic vascular resistance (SVR) in 20 normotensive subjects (n: AA=6 and GG=14). Results: We found that the GG genotype had higher Epi and Epi/NE when compared to AA (Epi=98±21 vs. 53±10pg/l; NE= 344±56 vs. 462±79pg/l; Epi/NE= 0.31±0.07 vs. 0.13±0.03, for GG and AA, respectively, mean±SE, p&lt;0.05 for Epi and Epi/NE). We found no differences between the genotype groups in 24hr. renal Na + handling (serum Na + , urine Na + , or F E Na). We found no differences in HR, SBP, or SV between the groups. The GG group had a trend towards a lower DBP, and MAP, but these did not reach statistical significance (DBP= 70±3 vs. 75±2mmHg; MAP= 83±3 vs. 87±2mmHg, for GG and AA, respectively, mean±SE). The GG group had a higher Q and a lower SVR when compared to the AA group (Q= 6.0±0.5 vs. 4.8±0.4 l/min; SVR= 1020±64 vs. 1316±95 dynes*sec/cm 5 , for GG and AA, respectively mean±SE, p&lt;0.05). Conclusion: These results suggest that genetic variation of PNMT can influence resting blood pressure in normotensive individuals and that this may be the result of cardiovascular function, rather than renal Na + handling.
The soluble guanylate cyclase stimulator IW-1973 prevents inflammation and fibrosis in experimental non-alcoholic steatohepatitis
Authors: R. Flores-Costa, J. Alcaraz-Quiles, E. Titos, C. López-Vicario, M. Casulleras, M. Duran-Güell, B. Rius, A. Diaz, K. Hall, C. Shea, R. Sarno, J.L. Masferrer, J. Claria
Journal: Journal of Hepatology (2017)
Prognostic value and prediction of extra-tumoral microvascular invasion among patients who candidate for hepatectomy or liver transplantation for hepatocellular carcinoma
Authors: H. Nitta, M.-A. Allard, G. Pittau, O. Ciacio, E. Vibert, A.S. Cunha, D. Cherqui, D. Castaing, H. Bismuth, H. Baba, R. Adam
Journal: Journal of Hepatology (2017)
Poor investment in child mental health research should not be tolerated
Authors: Eilis M Kennedy, Rob Senior
Journal: BMJ (2017)

Wolpert and colleagues highlight the limitations of the current evidence base for treatment in child mental health.1 That child mental health is “everybody’s business”2 has long been the mantra of clinicians working in the field, so recognising the pivotal role of the wider community in children’s wellbeing is uncontroversial, but we must also focus on increasing …
Rate and predictive factors of spontaneous hepatitis C virus clearance after acute infection in human immunodeficiency virus-positive subjects
Authors: M. Merli, L. Galli, A. Poli, S. Salpietro, E. Messina, M.R. Parisi, A. Andolina, G. Morsica, S. Bagaglio, A. Castagna, A. Lazzarin, C. Uberti-Foppa, H. Hasson
Journal: Journal of Hepatology (2017)
Echocardiography in patients with cirrhosis does not predict the clinical outcome after Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPSS)
Authors: M.J. Armstrong, F. Gohar, G. Baker, P. Nightingale, D. Greaves, A. Dhaliwal, H. Mehrzad, S. Olliff, D. Schmidt, R. Steeds, D. Tripathi
Journal: Journal of Hepatology (2017)
Abstract 215: Does the Relation of CPR Performer to Victim Affect Survival of Out-of-Hospital Cardiac Arrest?
Authors: Hideo Inaba, Yoshio Tanaka, Daiki Nishi, Yutaka Takei, Miki Enami, Yoshikazu Goto
Journal: Circulation (2011)

Backgrounds and Aim Early cardiopulmonary resuscitation (CPR) with a considerable quality is essential for survival of out-of-hospital cardiac arrests (OHCAs). The present study was conducted to test our hypothesis that relation of CPR performer to cardiac arrest victim may affect the survival of out-of-hospital cardiac arrests (OHCAs). Methods Data from 2068 OHCAs with CPR before emergency medical technician arrival, that occurred at other locations than care facilities from April, 2003 to March, 2010 in Ishikawa prefecture, were prospectively collected and analyzed. The performers of CPR were categorized into 4 groups; family and relatives, friends, strangers and healthcare providers. The backgrounds, characteristics and outcomes of OHCAs were compared among the 4 groups and between family and other 3 or 2 groups. Results (see Table) Family and relatives were less frequently the CPR performers in witnessed OHCAs, and were more frequently the CPR performers in OHCAs that occurred at home. They more frequently initiate the CPR following telephone-CPR and perform chest compression-only CPR. When analyzed collectively for all OHCAs, family member or relative as a CPR performer was associated with poor outcomes. When analyzed for subgroups of OHCAs, the effects of relations to victim were significant only for unwitnessed OHCAs and the OHCAs that occurred at other locations than home. Critical time factors related to survival did not significantly differ among or between the groups. Multiple logistic regression analysis for OHCAs that occurred at other locations than home, but not for all OHCAs, disclosed that family member or relative as a CPR performer is an independent factor associated with 1-Y survival. Conclusions The relations to victims dependently affect the outcomes of OHCAs. Although the quality of CPR was not determined in this study, this observation should be considered to plan a better strategy for improving the quality of CPR and outcomes of OHCAs.
Hepatic expression of lysosomal acid lipase is reduced in non-alcoholic fatty liver disease and inversely associated with the degree of microvescicular steatosis, impairment of the autophagic process and NAFLD activity score
Authors: U. Vespasiani-Gentilucci, F. Valentini, S. Carotti, F. Vorini, M. Zingariello, M. Francesconi, G. Galati, P. Gallo, A. De Vincentis, C. Dell’Unto, S. Morini, A. Picardi
Journal: Journal of Hepatology (2017)
Afatinib for patients with advanced NSCLC pretreated with chemotherapy and an EGFR tyrosine kinase inhibitor: Retrospective analysis of the Swiss Afatinib Named Patient Program
Authors: M. Ehmann, L. Wannesson, M. Pless, M. Früh, O. Gautschi, A. Curioni-Fontecedro, D. Betticher, M. Mark, A. Ochsenbein, S.I. Rothschild
Journal: Annals of Oncology (2017)
Effects of probiotics (Lactobacillus rhamnosus R0011 and Lactobacillus acidophilus R0052) in the treatment of mild alcoholic hepatitis: randomized controlled multicenter study
Authors: K.T. Suk, D.J. Kim, Y.J. Yang, M. Hong, S.E. Kim, J.W. Park, H.S. Kim, M.K. Jang, C.K. Park
Journal: Journal of Hepatology (2017)
Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma
Authors: A. Arbelaiz, M. Azkargorta, Á. Santos-Laso, M.J. Perugorria, O. Erice, E. Gonzalez, A. Lapitz, L. Izquierdo, P. Olaizola, P.Y. Lee, A. Arregi, R. Jimenez-Aguero, A. Lacasta, C. Ibarra, A. Sánchez-Campos, J.P. Jimeno, M. Krawczyk, F. Lammert, M. Marzioni, R. Macias, J.J. Marín, T. Patel, G. Gores, I. Martinez, F. Elortza, J.M. Falcón-Pérez, L. Bujanda, J.M. Banales
Journal: Journal of Hepatology (2017)
A Ferroelectric Ceramic/Polymer Composite‐Based Capacitive Electrode Array for In Vivo Recordings
Authors: Changyong Chen, Miaomiao Xue, Yige Wen, Guang Yao, Yan Cui, Feiyi Liao, Zhuocheng Yan, Long Huang, Saeed Ahmed Khan, Min Gao, Taisong Pan, Hulin Zhang, Wei Jing, Daqing Guo, Sanfeng Zhang, Hailiang Yao, Xiong Zhou, Qiang Li, Yang Xia, Yuan Lin
Journal: Advanced Healthcare Materials (2017)

A new implantable capacitive electrode array for electrocorticography signal recording is developed with ferroelectric ceramic/polymer composite. This ultrathin and electrically safe capacitive electrode array is capable of attaching to the biological tissue conformably. The barium titanate/polyimide (BaTiO 3 /PI) nanocomposite with high dielectric constant is successfully synthesized and employed as the ultrathin dielectric layer of the capacitive BaTiO 3 /PI electrode array. The performance of the capacitive BaTiO 3 /PI electrode array is evaluated by electrical characterization and 3D finite‐element modeling. In vivo, neural experiments on the visual cortex of rats show the reliability of the capacitive BaTiO 3 /PI electrode array. This work shows the potentials of capacitive BaTiO 3 /PI electrode array in the field of brain/computer interfaces.
Evaluation of gum mastic (Pistacia lentiscus) as a microencapsulating and matrix forming material for sustained drug release
Authors: Dinesh M. Morkhade
Journal: Asian Journal of Pharmaceutical Sciences (2017)

In this study, a natural gum mastic was evaluated as a microencapsulating and matrix-forming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium (DFS) and diltiazem hydrochloride (DLTZ) were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules with DFS. Particle size and drug loading of microparticles was in the range of 22-62 µm and 50-87%, respectively. Increase in mastic: drug ratio increased microparticle size, improved drug loading and decreased the drug release rate. Microparticles with gum: drug ratio of 2:1 could sustain DLTZ release up to 12 h and released 57% DFS in 12 h. Mastic produced tablets with acceptable pharmacotechnical properties. A 30% w/w of mastic in tablet could sustain DLTZ release for 5 h from wet granulation, and DFS release for 8 h and 11 h from wet and melt granulation, respectively. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and microparticles for sustained drug release.
JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias
Authors: C Delgado-Martin, L K Meyer, B J Huang, K A Shimano, M S Zinter, J V Nguyen, G A Smith, J Taunton, S S Winter, J R Roderick, M A Kelliher, T M Horton, B L Wood, D T Teachey, M L Hermiston
Journal: Leukemia (2017)

While outcomes for children with T-cell acute lymphoblastic leukemia (T-ALL) have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid (GC) resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs as well as in a subset of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 (IL7) stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.
Patients above 65 years of age achieved the same SVR12 as younger patients despite increased comorbidities: findings from a large real-world, multi-country, observational cohort of 12-week ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin
Authors: R. Flisiak, A. Maieron, M. Kraus, V. Leroy, Y. Horsmans, B. Hunyady, S. Norris, M. Bondin, D. Latarska-Smuga, A.P. dos Santos, M. Martinez-Tristani, B. Conway
Journal: Journal of Hepatology (2017)
A2a receptor stimulation prevents the multiple processes that lead to hepatic “immuno-lipotoxicity” in mice fed with MCD diet and blocks non-alcoholic steatohepatitis development
Authors: E. Alchera, S. Rolla, C. Imarisio, V. Bardi, G. Valente, F. Novelli, R. Carini
Journal: Journal of Hepatology (2017)
On-treatment ALT flares are associated with HBsAg loss in genotype A chronic hepatitis B-infected patients treated with nucleotide analogue therapy
Authors: D. Wong, R. Walsh, R. Hammond, L. Yuen, P. Revill, A. Gaggar, M. Subramanian, K. Kitrinos, S. Locarnini, A. Thompson
Journal: Journal of Hepatology (2017)
Prospective comparison of shear-wave elastography, CAP and conventional ultrasound for non-invasive detection and grading of steatosis
Authors: M. Ronot, P.-E. Rautou, M.Di. Burgio, A. Payencé, P. Bedossa, V. Paradis, C. Francoz, O. Nekachtali, F. Durand, V. Vilgrain, L. Castera
Journal: Journal of Hepatology (2017)
Phase I study of margetuximab (MGAH22), an FC-modified chimeric monoclonal antibody (MAb), in patients (pts) with advanced solid tumors expressing the HER2 oncoprotein.
Authors: Howard A. Burris, Giuseppe Giaccone, Seock-Ah Im, Todd Michael Bauer, Jane B. Trepel, Jeffrey L. Nordstrom, Hua Li, David A Carlin, Jan E. Baughman, Stanford Stewart, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2013)

3004 Background: The anti-HER2 MAb, trastuzumab (H), has proven effective for HER2+ breast cancer (BC) and gastroesophageal cancer (GEC). H’s mechanism of action is incompletely understood, but evidence indicates ADCC is important. MGAH22 is an Fc-modified chimeric MAb which preserves the antigen binding properties of H, and exhibits enhanced binding to the activating low affinity Fcg receptor, CD16A, and diminished binding to the inhibitory low affinity Fcg receptor, CD32B. Preclinical data indicate MGAH22 is more potent than H. Methods: 34 pts with HER2 positive (2+ or 3+ by IHC) tumors have been treated: 19 in 5 dose-escalation cohorts (0.1 - 6.0 mg/kg qw x 4); 15 in 6.0 mg/kg expansion. Tumor types include: BC (10), GEC (13), colon (5), lung (2), salivary (1), ampulla of Vater (1), endometrium (1), bladder (1). Results: MGAH22 was well tolerated. Most common adverse events (AEs) were Grade 1-2 constitutional symptoms and infusion-related reactions. Related AEs ≥ Grade 3 were limited to a single infusion reaction, 2 episodes of brief lymphopenia confounded by steroids, and transient worsening anemia. No cardiac toxicities were observed. Dose escalation was halted at 6 mg/kg, well above the preclinically predicted minimally effective dose (0.1 mg/kg). Antitumor activity has been observed at all dose levels, including partial responses (PRs) and long times to progression (≥ 5 mo). Two PRs lasting 3.5 and 5.5 mo were observed among the 10 BC pts (both had failed prior H and lapatinib). 4/13 GEC pts experienced stable disease lasting a median of 3.6 mo (range 1.5–5.3), all but one previously failing anti-HER2 treatment. Conclusions: Margetuximab is well tolerated with promising activity in pts with BC and GEC who have failed prior HER-2 therapies and in pts with HER2+ tumors for which H is considered ineffective. A phase II trial in relapsed or refractory HER2 2+, nonamplified BC is underway. Clinical trial information: NCT01195935. [Table: see text]
Hearing Focuses on Proposed Cuts in Cancer Research
Authors: Jeff Lyon
Journal: JAMA (2017)

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Role of endoscopic biliary drainage in advanced hepatocellular carcinoma with jaundice
Authors: H.Y. Woo, S.Y. Han, J. Heo, S.Y. Park, W.Y. Tak, Y.M. Hong, K.T. Yoon, D.U. Kim, D.H. Baek, M. Cho
Journal: Journal of Hepatology (2017)
Whole genome deep sequencing is superior to sequencing only regions of special interest for the characterization of HDV evolution
Authors: F. Wellhöner, A. Wranke, I. Barrantes, I. Plumeier, B. Bremer, M.P. Manns, D.H. Pieper, H. Wedemeyer, B. Heidrich, A.G. Heidrich
Journal: Journal of Hepatology (2017)
Osteoprotegerin production and profibrotic activity in liver fibrosis are TGFβ dependent
Authors: A. Adhyatmika, K.S.S. Putri, L. Beljaars, E. Gore, K.A. Mangnus, C. Reker-Smit, E. Post, K. Poelstra, P. Olinga, B.N. Melgert
Journal: Journal of Hepatology (2017)
Abstract 185: Chromogranin A is a Potent Prognostic Biomarker in Acute Heart Failure, and its Fragment Catestatin Regulates Cardiomyocyte Calcium Homeostasis by Camkiiδ Inhibition
Authors: Anett Hellebø Ottesen, Cathrine R. Carlson, William E. Louch, Rune Forstrøm Johansen, Mats Stridsberg, Hilde Jarstadmarken, Magnar Bjørås, Arne Didrik Høiseth, Jon Brynildsen, Torbjørn Omland, Geir Christensen, Helge Røsjø
Journal: Circulation Research (2015)

Background: Circulating chromogranin A (CgA) levels have been found associated with clinical outcomes in cardiovascular disease, but whether the CgA fragment catestatin (CST) may directly modulate cardiomyocyte Ca 2+ handling is not known. Methods: The prognostic utility of circulating CgA levels were compared between patients with acute HF (n=143) and chronic acute obstructive pulmonary disease (COPD, n=84). Functional effects of CST were assessed in isolated cardiomyocyte and explanted hearts. Results: CgA levels were associated with mortality in acute HF patients, but not in acute COPD. (Figure; patients stratified according to CgA quartiles on hospital admission). Admission CgA levels were also associated with mortality after adjusting for other risk factors in multivariate analysis. We found CST to interact with Ca 2+ /calmodulin (CaM)-dependent protein kinase II δ (CaMKIIδ) and to inhibit CaMKIIδ activity. CST also reduced CaMKIIδ-dependent phosphorylation of the ryanodine receptor 2 and phospholamban. In line with CaMKIIδ inhibition, CST reduced Ca 2+ spark and wave frequency, attenuated Ca 2+ sparkdimensions, increased sarcoplasmic reticulum Ca 2+ content, andaugmented magnitude and kinetics of cardiomyocyte Ca 2+ transients and contractions. Frequency dependent acceleration of relaxation was most pronounced in the Control group, an indication of CaMKIIδ activation, and this was attenuated by CST. Conclusions: CgA regulates cardiomyocyte Ca 2+ handling via CaMKIIδ inhibition, which makes CgA an interesting CV biomarker and potential compensatory mechanism in situations of enhanced CaMKIIδ activity.
Concordant Underexpression of Fanconi Anemia/BRCA1 Pathway Proteins in a Major Proportion of Myelodysplastic Syndromes
Authors: Fatemeh Majidi, Judith Neukirchen, Ulrich Germing, Ron-Patrick Cadeddu, Stefan Braunstein, Rainer Haas, Norbert Gattermann
Journal: Blood (2016)
Regulation of Bcl-2 expression by sumoylation
Authors: Zhaohui Lu, Hailong Wu, Yin-Yuan Mo
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4074 

Bcl-2 is an anti-apoptotic protein involved in oncogenesis and chemoresistance. expression of Bcl-2 is regulated by many factors. We have previously shown that suppression of sumoylation by a dominant negative Ubc9 mutant (Ubc9-DN) in the estrogen receptor (ER) positive MCF-7 cells leads to alterations of tumor cell’s drug responsiveness as well as tumor growth in a xenograft mouse carcinoma model. Gene profiling analysis suggests that a dozen of estrogen receptor (ER)-mediated genes are down regulated in the Ubc9-DN cells; the most significantly decreased gene is Bcl-2. To determine whether Ubc9 regulates Bcl-2 expression dependent upon ER, we generated stable Ubc9-DN transfectants in the ER negative tumor cell line MDA-MB-231. In contrast to the ER positive MCF-7 cells, we found that Ubc9 had no effect of Bcl-2 expression in MDA-MB-231 cells. Furthermore, luciferase assays using the ER response element (ERE) construct indicated that ERE activity was also decreased in the Ubc9-DN MCF-7 cells. Similar to the Bcl-2 mRNA and protein levels, we also found that the Bcl-2 promoter activity was reduced in the Ubc9-DN MCF-7 cells. Suppression of ER by siRNA and ER antagonist raloxifene reduced expression of Bcl-2. Moreover, raloxifene could suppressed the Bcl-2 promoter activity in a dose-dependent and time-dependent manner. Steroid hormone receptor coactiviator-1 (SRC-1) was previously shown to sumoylated, whereby it stimulated ER-mediated gene expression by prolonging its nuclear presence. Consistent with this, we found that SRC-1 was localized in the cytoplasm of the Ubc9-DN MCF-7 cells whereas it was predominantly in the perinuclear region of the Ubc9-WT MCF-7 cells, suggesting that Ubc9 affects the subcellular localization of SRC-1. In addition, the expression level of SRC-1 was also lower in Ubc9-DN cells than in the Ubc9-WT cells. Assays with the proteasome inhibitor MG132 suggested that Ubc9-DN also reduced the stability of SRC-1, whereas mutations at the SUMO sites SRC-1 decreased its stability. These results suggest that Ubc9 may regulate Bcl-2 expression in ER-positive cells through SRC-1. (Supported in part by CA102630 from NIH)