tbuckley/cabot-search huggingface dataset:
Barry John Cooper
Authors: Louise Cooper
Journal: BMJ (2018)

Barry John Cooper was born in Birmingham. He had an early talent for languages and won a trip to France in a French competition at 16 while at Handsworth Grammar School. He was the first in his family to go to university and took his BA in Russian. To the surprise of his mother he then announced that he wanted to study medicine. 

He gained his medical degree from the University of Birmingham in 1961. He had already passed his LRCP and MRCS several months earlier, in order to start working. After …
Abstract 15761: Outcomes After Ablation And Cardioversion in Patients With Non-valvular Atrial Fibrillation: Results From the XANTUS Study
Authors: A.John Camm, Alexander G.G Turpie, Susanne Hess, Pierre Amarenco, Silvia Kuhls, Sylvia Haas, Martin van Eickels, Paulus Kirchhof
Journal: Circulation (2016)

Introduction: Catheter ablation and cardioversion are standard care for re-establishing sinus rhythm in patients with non-valvular atrial fibrillation (AF) but carry a risk of periprocedural thromb...
Circadian Variation of Paroxysmal Atrial Fibrillation
Authors: TakeshiYamashita, YujiMurakawa, KazunoriSezaki, MasashiInoue, NoriyukiHayami, YutakaShuzui, MasaoOmata
Journal: Circulation (1997)

Background Circadian variation in the incidence of acute cardiovascular events is well known but has not been extensively investigated in paroxysmal atrial fibrillation, although the significance of this arrhythmia is growing in our society with the increasing number of aged people. Methods and Results We detected 150 patients with paroxysmal atrial fibrillation in a drug-free state from among 25 500 consecutive Holter recordings. To determine whether the onset, maintenance, and termination of paroxysmal atrial fibrillation were random events, we analyzed the total recorded duration of arrhythmia and the incidence of and number of patients with the onset, maintenance, and termination of this arrhythmia as hourly data and as hourly probabilities. A prominent circadian rhythm of the total duration of atrial fibrillation, ≈90% of which was well explained by a single cosinusoidal function, was detected with a nadir around 11 am. Because the onset of the arrhythmia had little or no circadian rhythm, this findi...
Association of Low-Grade Albuminuria With Adverse Cardiac Mechanics
Authors: Daniel H. Katz, Senthil Selvaraj, Frank G. Aguilar, Eva E. Martinez, Lauren Beussink, Kwang-Youn A. Kim, Jie Peng, Jin Sha, Marguerite R. Irvin, John H. Eckfeldt, Stephen T. Turner, Barry I. Freedman, Donna K. Arnett, Sanjiv J. Shah
Journal: Circulation (2013)

Background— Albuminuria is a marker of endothelial dysfunction and has been associated with adverse cardiovascular outcomes. The reasons for this association are unclear but may be attributable to the relationship between endothelial dysfunction and intrinsic myocardial dysfunction. Methods and Results— In the Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and family-based study of hypertension, we examined the relationship between urine albumin-to-creatinine ratio (UACR) and cardiac mechanics (n=1894, all of whom had normal left ventricular ejection fraction and wall motion). We performed speckle-tracking echocardiographic analysis to quantify global longitudinal, circumferential, and radial strain, and early diastolic (e′) tissue velocities. We used E/e′ ratio as a marker of increased left ventricular filling pressures. We used multivariable-adjusted linear mixed effect models to determine independent associations between UACR and cardiac mechanics. The mean age was 50±14 years, 59% were female, and 46% were black. Comorbidities were increasingly prevalent among higher UACR quartiles. Albuminuria was associated with global longitudinal strain, global circumferential strain, global radial strain, e′ velocity, and E/e′ ratio on unadjusted analyses. After adjustment for covariates, UACR was independently associated with lower absolute global longitudinal strain (multivariable-adjusted mean global longitudinal strain [95% confidence interval] for UACR Quartile 1 = 15.3 [15.0–15.5]% versus UACR Q4 = 14.6 [14.3–14.9]%, P for trend &lt;0.001) and increased E/e′ ratio (Q1 = 25.3 [23.5–27.1] versus Q4 = 29.0 [27.0–31.0], P =0.003). The association between UACR and global longitudinal strain was present even in participants with UACR &lt; 30 mg/g ( P &lt;0.001 after multivariable adjustment). Conclusions— Albuminuria, even at low levels, is associated with adverse cardiac mechanics and higher E/e′ ratio.
Abstract 17517: Impact of Coronary Calcification Morphology on Acute Coronary Syndrome Presenting as a Non-ruptured Plaque at the Culprit Site
Authors: Shunsuke Miyauchi, Masaya Kato, Keigo Dote, Shota Sasaki, Noboru Oda
Journal: Circulation (2016)

Introduction: Previous pathological and computed tomography studies have revealed that vulnerable plaques exhibit a high frequency of spotty calcification. Some studies have also indicated that spo...
Abstract 19357: Mechanisms of Tobacco Products Induced Exacerbation of Atherosclerosis
Authors: Marina V Malovichko, Abhinav Agarwal, Srinivas D Sithu, Iris Zeller, Millicent Winner, Michelle E Smith, Nalinie S Wickramasinghe, Aruni Bhatnagar, Daniel J Conklin, Sanjay Srivastava
Journal: Circulation (2016)

Smoking has been shown to exacerbate atherosclerosis; however it is unclear which constituents of tobacco smoke/products aggravate atherogenesis. Smokeless tobacco (ST) and mainstream cigarette smo...
Differential Expression of Voltage-Gated K+ Channel Genes in Left Ventricular Remodeled Myocardium After Experimental Myocardial Infarction
Authors: MadhaviGidh-Jain, BoyuHuang, PraveerJain, NabilEl-Sherif
Journal: Circulation Research (1996)

Left ventricular (LV) remodeling after experimental myocardial infarction (MI) is associated with hypertrophy of noninfarcted myocardium and electrophysiological alterations. We have recently shown that post-MI hypertrophied LV myocytes have prolonged action potential duration (APD) and generate triggered activity from early afterdepolarizations. The prolonged APD was attributed to decreased density of the two outward K+ currents, Ito-fast (Ito-f) and Ito-slow (Ito-s), rather than changes in the density and/or kinetics of the L-type Ca2+ current. The changes in ionic current density may be related to alterations in the expression and levels of ion channel proteins. To test this hypothesis, rats underwent either left anterior descending coronary artery (LAD) ligation (post-MI group [n=10]) or sham surgery (sham group [n=10]). Three weeks later, transcripts from the noninfarcted LV myocardium in the post-MI group (n=6) and LV myocardium of the sham group (n=6) were analyzed by RNase protection assay. Expres...
Impact of Cilostazol on Restenosis After Percutaneous Coronary Balloon Angioplasty
Authors: EtsuoTsuchikane, AtsunoriFukuhara, TohruKobayashi, MotohiroKirino, KeitaYamasaki, TomokoKobayashi, MasahiroIzumi, SatoruOtsuji, HitoneTateyama, MakotoSakurai, NobuhisaAwata
Journal: Circulation (1999)

Background—Restenosis after percutaneous transluminal coronary (balloon) angioplasty (PTCA) remains a major drawback of the procedure. We previously reported that cilostazol, a platelet aggregation inhibitor, inhibited intimal proliferation after directional coronary atherectomy and reduced the restenosis rate in humans. The present study aimed to determine the effect of cilostazol on restenosis after PTCA. Methods and Results—Two hundred eleven patients with 273 lesions who underwent successful PTCA were randomly assigned to the cilostazol (200 mg/d) group or the aspirin (250 mg/d) control group. Administration of cilostazol was initiated immediately after PTCA and continued for 3 months of follow-up. Quantitative coronary angiography was performed before PTCA and after PTCA and at follow-up. Reference diameter, minimal lumen diameter, and percent diameter stenosis (DS) were measured by quantitative coronary angiography. Angiographic restenosis was defined as DS at follow-up >50%. Eligible follow-up angi...
Abstract 1344: Autophagy contributes to therapeutic resistance in head and neck cancer
Authors: Jaimee Eckers, Justin Skiba, Gopika Senthilkumar, Kwang P. Nickel, Adam D. Swick, Randall J. Kimple
Journal: Cancer Research (2018)

Abstract Background: In the curative setting for head and neck cancer (HNC) a common treatment is radiation combined with cetuximab, an antibody therapeutic targeting EGFR. Despite decades of research into improved treatments, therapeutic resistance remains a major challenge for this malignancy, with roughly 40% of patients developing recurrent disease. Recent evidence has suggested that autophagy, a cellular stress response, may be an additional contributor to therapy resistance, by protecting HNC cells from the cytotoxic effects of radiotherapy and the growth inhibitory effects of anti-EGFR treatment. The mechanism of radiation-induced autophagy is under current investigation. Methods: Cell lines were source from commercial sources, cultured under recommended conditions, and identity confirmed by short tandem repeat testing. Induction of autophagy was detected by immunoblot flux assays for LC3 and p62, immunofluorescent staining of autophagic vesicles, LC3 reporter flux assay, and flow cytometry using acridine orange. The effect of autophagy inhibition was tested using clonogenic survival assays. Induction of apoptosis was analyzed by immunoblot against cleaved caspase and PARP and via AnnexinV staining. Results: We evaluated a panel of both human papillomavirus (HPV) positive and negative HNC cell lines for autophagic response to both cetuximab (CTX) treatment and ionizing radiation (XRT). Flux assays revealed that both CTX and XRT treatment induced autophagy in a time- and dose-dependent manner. Immunofluorescent staining of LC3 to identify autophagic vesicles showed that a relatively small fraction of the total cell population is able to induce this response. Flow cytometry analysis demonstrated that autophagic cells were largely non-apoptoic. For example, in the UM-SCC47 cell line treated with CTX for 48 h, flow cytometry for autophagy (20.8%), apoptosis (13.7%) or dual staining (5.4%) suggests a cytoprotective role for autophagy. The addition of the ULK1 inhibitor, SBI-0206965) to CTX and XRT induced apoptosis as shown by caspase activity and AnnexinV staining and reduced clonogenic cell survival. Conclusions: These preclinical studies have established the proof of concept for the cytoprotective effect of autophagy in response to anticancer treatments including EGFR inhibition and radiotherapy in HNC. Further, we have identified the addition of specific autophagy inhibitors to standard treatments as a potential strategy to overcome this mechanism of resistance. Citation Format: Jaimee Eckers, Justin Skiba, Gopika Senthilkumar, Kwang P. Nickel, Adam D. Swick, Randall J. Kimple. Autophagy contributes to therapeutic resistance in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1344.
Abstract 5563: Kinetically-controlled release of blocking molecules for the targeted enhancement of therapeutic activity in antibody-cytokine fusion proteins
Authors: Tiziano Ongaro, Martina Bigatti, Filippo Sladojevich, Etienne Donckele, Alessandra Micaela Villa, Dario Neri
Journal: Cancer Research (2018)

Abstract Cytokines are able to mediate a potent anticancer activity but have significant side effects that prevent dose escalation to therapeutically-active regimens. Targeting the cytokines to the site of disease helps to improve their therapeutic index while decreasing associated toxicities. However, peak concentrations in blood are still associated with side-effects. We have developed a novel technology (termed “CORK Technology”), which consists in masking the undesired activity of a cytokine in circulation. The “cork” can be either an antibody fragment or a small molecule, which specifically binds to the cytokine thus preventing the interaction with its receptor. Once the complex accumulates in the tumor, the cork dissociate from the cytokine allowing it to exert its function. Capitalizing on the fact that the kinetic dissociation constant koff of the complex is identical in different species, this technology can be easily translated from mouse to man with comparable results. In this poster we describe the experimental implementation of CORK Technology to improve the therapeutic index of the clinical stage L19-IL2 (L19 is an antibody fragment specific to the alternatively-spliced EDB domain of fibronectin, a marker of tumor angiogenesis). Two classes of IL2 inhibitors were discovered and characterized: (i) a fully human scFv fragment, and (ii) a small organic ligand, featuring a modified methylindole moiety. Both types of agents reduced IL2 activity in vitro, were able to dissociate from the cognate cytokine in a kinetically-tuned process and allowed the administration of the L19-IL2 fusion protein at higher doses, both in normal and in tumor-bearing mice. The technology is applicable to other cytokine payloads and facilitates the development of targeted cytokine products with “activity on demand” (i.e., with increased activity at the tumor site, promoting an activation and proliferation of tumor-resident lymphocytes). Albeit still in its infancy, this elegant approach provides promising results and a strong rationale to further investigate this therapeutic power of the CORK Technology. Citation Format: Tiziano Ongaro, Martina Bigatti, Filippo Sladojevich, Etienne Donckele, Alessandra Micaela Villa, Dario Neri. Kinetically-controlled release of blocking molecules for the targeted enhancement of therapeutic activity in antibody-cytokine fusion proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5563.
Distinct Role of cAMP and cGMP in the Cell Cycle Control of Vascular Smooth Muscle Cells
Authors: ShinyaFukumoto, HidenoriKoyama, MasayukiHosoi, KenjiroYamakawa, ShinjiTanaka, HirotoshiMorii, YoshikiNishizawa
Journal: Circulation Research (1999)

Abstract—cAMP and cGMP are known to suppress vascular smooth muscle cell (SMC) proliferation. In this study, our aim was to delineate the molecular mechanism underlying cAMP and cGMP suppression of cell cycle transition in human SMCs. cAMP inhibits both platelet-derived growth factor–stimulated cyclin-dependent kinase (cdk) 2 and cdk4 activation through upregulation of the cdk2 inhibitor p27Kip1 and downregulation of cyclin D1 expression, which leads to a complete arrest of the cells in phase G1. In contrast, cGMP inhibits cyclin D1 expression, inhibits cdk4 activation, and delays platelet-derived growth factor–mediated cdk2 activation, resulting in a delay in G1/S transition. A transient increase in p27Kip1 in cdk2 immunoprecipitates, without changes in total cellular p27Kip1 levels, correlates with the delay in cdk2 activation caused by cGMP. Thus, cAMP and cGMP differentially affect cell cycle through distinct regulation of cell cycle molecules in human SMCs.
Abstract 2004: Identification of MLK4 as a novel regulator of cancer stem cells in triple-negative breast cancer
Authors: Chang-Ching Lin, Miao-Chia Lo, Rebecca Moody, Nicholas Stevers, Samantha Tinsley, Mari Gasparyan, Max Wicha, Duxin Sun
Journal: Cancer Research (2018)

Abstract Cancer stem cells (CSCs) are a small population of cancer cells that are capable of self-renewal and tumor initiation. As a result, targeting CSCs is a potential therapeutic strategy for preventing cancer relapse and metastasis. Mixed lineage kinase 4 (MLK4), a serine/threonine kinase, is known to regulate mesenchymal glioma stem cells and to drive tumorigenesis in colorectal cancer. We found that MLK4 was highly expressed in triple-negative breast cancer (TNBC) compared to other breast cancer subtypes according to the database from The Cancer Genome Atlas. Furthermore, multiple datasets indicated that higher expression of MLK4 was associated with poor prognosis in breast cancer. Despite the correlation of MLK4 and clinical outcome, the function of MLK4 in breast cancer is still not known. In this study, we found that knockdown of MLK4 significantly decreased secondary mammosphere formation, the CD44+/CD24- CSC population, invasion and migration in TNBC cell lines. In addition to suppressing CSC phenotypes in vitro, knockdown of MLK4 also inhibited tumor growth in NOD/SCID mice. Secondary transplantation of tumor cells demonstrated that silencing of MLK4 significantly decreased tumor-initiating cell frequency. As accessed by qPCR, knockdown of MLK4 led to decreased expression of mesenchymal genes (CD44 and VIM) and concomitant increased expression of epithelial genes (CDH1 and claudin genes). Immunohistochemical staining revealed that knockdown of MLK4 in xenografts resulted in increased expression of CK19, a luminal-epithelial marker. These studies indicate that MLK4 plays an important role in the function of mesenchymal-like CSCs in TNBC. Silencing of MLK4 in TNBC cell lines can transform CSC in these tumors to a more differentiated epithelial cell state. Together, these studies identify that MLK4 is a potential therapeutic target for CSCs in TNBC. Citation Format: Chang-Ching Lin, Miao-Chia Lo, Rebecca Moody, Nicholas Stevers, Samantha Tinsley, Mari Gasparyan, Max Wicha, Duxin Sun. Identification of MLK4 as a novel regulator of cancer stem cells in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2004.
The Oslo Diet-Heart Study
Authors: Paulleren
Journal: Circulation (1970)

The study deals with 412 men, aged 30 to 64 years, randomized 1 to 2 years after a first myocardial infarction. For the experimental group a diet low in saturated fats and cholesterol, and high in polyunsaturated fats was recommended. After 5 years, as reported previously, the incidence of fatal and nonfatal myocardial reinfarction was found to be significantly reduced. Sudden  was uninfluenced. Major coronary heart disease (CHD) relapses, including fatal and nonfatal events (MI), were significantly reduced (P = 0.05). After 11 years, death from all causes had occurred in 101 of the original dieters and 108 controls. A significantly reduced myocardial infarction mortality in the original diet group was found (32 versus 57, P = 0.004). The total number of coronary deaths (fatal myocardial infarction and sudden death) was 79 in the diet group and 94 in the control group (P = 0.097). The CHD mortality was correlated with age, serum cholesterol level, blood pressure, body weight, smoking habits, and a ...
Predictive Low-Glucose Suspend Reduces Hypoglycemia in Adults, Adolescents, and Children With Type 1 Diabetes in an At-Home Randomized Crossover Study: Results of the PROLOG Trial
Authors: Gregory P. Forlenza, Zoey Li, Bruce A. Buckingham, Jordan E. Pinsker, Eda Cengiz, R. Paul Wadwa, Laya Ekhlaspour, Mei Mei Church, Stuart A. Weinzimer, Emily Jost, Tatiana Marcal, Camille Andre, Lori Carria, Vance Swanson, John W. Lum, Craig Kollman, William Woodall, Roy W. Beck
Journal: Diabetes Care (2018)

This study evaluated a new insulin delivery system designed to reduce insulin delivery when trends in continuous glucose monitoring (CGM) glucose concentrations predict future hypoglycemia.Individuals with type 1 diabetes (n = 103, age 6-72 years, mean HbA1c 7.3% [56 mmol/mol]) participated in a 6-week randomized crossover trial to evaluate the efficacy and safety of a Tandem Diabetes Care t:slim X2 pump with Basal-IQ integrated with a Dexcom G5 sensor and a predictive low-glucose suspend algorithm (PLGS) compared with sensor-augmented pump (SAP) therapy. The primary outcome was CGM-measured time <70 mg/dL.Both study periods were completed by 99% of participants; median CGM usage exceeded 90% in both arms. Median time <70 mg/dL was reduced from 3.6% at baseline to 2.6% during the 3-week period in the PLGS arm compared with 3.2% in the SAP arm (difference [PLGS - SAP] = -0.8%, 95% CI -1.1 to -0.5, P < 0.001). The corresponding mean values were 4.4%, 3.1%, and 4.5%, respectively, represent-ing a 31% reduction in the time <70 mg/dL with PLGS. There was no increase in mean glucose concentration (159 vs. 159 mg/dL, P = 0.40) or percentage of time spent >180 mg/dL (32% vs. 33%, P = 0.12). One severe hypoglycemic event occurred in the SAP arm and none in the PLGS arm. Mean pump suspension time was 104 min/day.The Tandem Diabetes Care Basal-IQ PLGS system significantly reduced hypoglycemia without rebound hyperglycemia, indicating that the system can benefit adults and youth with type 1 diabetes in improving glycemic control.
Evidence for a Functional Role of Angiotensin II Type 2 Receptor in the Cardiac Hypertrophic Process In Vivo in the Rat Heart
Authors: ZoltánLakó-Futó, IstvánSzokodi, BalázsSármán, GáborFöldes, HeikkiTokola, MikaIlves, HannaLeskinen, OlliVuolteenaho, RékaSkoumal, RudolfdeChâtel, HeikkiRuskoaho, MiklósTóth
Journal: Circulation (2003)

Background— The precise function of angiotensin II type 2 receptor (AT2-R) in the mammalian heart in vivo is unknown. Here, we investigated the role of AT2-R in cardiac pressure overload. Methods and Results— Rats were infused with vehicle, angiotensin II (Ang II), PD123319 (an AT2-R antagonist), or the combination of Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72 hours. Ang II–induced increases in mean arterial pressure, left ventricular weight/body weight ratio, and elevation of skeletal α-actin and β-myosin heavy chain mRNA levels were not altered by PD123319. In contrast, AT2-R blockade resulted in a marked increase in the gene expression of c-fos, endothelin-1, and insulin-like growth factor-1 in Ang II–induced hypertension. In parallel, Ang II–stimulated mRNA and protein expression of atrial natriuretic peptide were significantly augmented by AT2-R blockade. Moreover, PD123319 markedly increased the synthesis of B-type natriuretic peptide. Furthermore, the expression...
Hypercholesterolemia Abrogates Late Preconditioning via a Tetrahydrobiopterin-Dependent Mechanism in Conscious Rabbits
Authors: Xian-LiangTang, HitoshiTakano, Yu-TingXuan, HiroshiSato, EitaroKodani, BuddhadebDawn, YanqingZhu, GreggShirk, Wen-JianWu, RobertoBolli
Journal: Circulation (2005)

Background— Although the late phase of ischemic preconditioning (PC) is known to confer cardioprotection in healthy animal models, it is unknown whether this phenomenon exists in the presence of hypercholesterolemia. The goal of this study was to determine whether the infarct-sparing effect of late PC is affected by hypercholesterolemia and, if so, whether a tetrahydrobiopterin (BH4)-dependent mechanism is responsible for the loss of late PC. Methods and Results— Conscious rabbits fed a normal diet or a 1% cholesterol diet for 6 weeks were subjected to ischemic PC (six 4-minute coronary occlusion/4-minute reperfusion cycles) and, 24 hours later, underwent a 30-minute occlusion followed by 3 days of reperfusion. A total of 125 rabbits were used. In normocholesterolemic rabbits, ischemic PC reduced infarct size, an effect that was abrogated by administration of the BH4 synthesis inhibitor N-acetylserotonin (15 mg/kg IV) before the 30-minute occlusion. In hypercholesterolemic rabbits, however, ischemic PC fa...