tbuckley/cabot-search huggingface dataset:
Abstract 10257: Nuclear Angiotensin-II Receptor Gene Expression in Cardiac Fibroblasts: Receptor Subtype-Specific Differential Role of IP-3-Receptor (IP3R) Related and Nitric Oxide Signaling
Authors: Artak Tadevosyan, Danny Del Duca, Yu Chen, Bruce G Allen, Stanley Nattel
Journal: Circulation (2011)

Introduction:  Angiotensin-II (Ang-II) is a crucial regulator of cardiac fibroblast (FB) structure and function. This study assessed whether activation of nuclear delimited AT1 (AT1R) and AT2 (AT2R) receptors in cardiac fibroblasts activates signalling events that influence gene expression.   Methods:  Canine atrial (Atr) and ventricular (Vt) FBs were isolated and intracellular localization of AT1R and AT2R assessed by immunofluorescence and Western blot. Intact nuclei were purified by differential centrifugation. Nitric oxide (NO) was detected with the fluorescent dye DAF-2.  De novo  RNA production was measured by transcription initiation assay ([α 32 P]UTP).   Results:  AT1R and AT2R proteins localized to nuclear membrane (immunohisto and immunoblot) and colocalized with nuclear markers TOPRO 3 and Histone 3. Purified nuclei contained high concentrations of DNA (Atr nuclei 2206±108* μ g/ml DNA vs cytosol 97±13; Vt nuclei 874±20* μ g/ml DNA vs cytosol 84±8, *P +  cpm/ng DNA and 148±8 +  cpm/ng DNA vs 69±9 cpm/ng DNA control; Vt: 260±21 +  cpm/ng DNA and 240±6 +  cpm/ng DNA vs 49±5 cpm/ng DNA control, n=5/group,  + P +  (Atr) and 48% +  (Vt) by the IP3R-blocker 2APB (but not L-NAME) and AT2R-mediated responses were reduced by 79% +  (Atr) and 29% +  (Vt) by L-NAME. Atr nuclei pretreated with both 2APB and L-NAME prior to Ang-II had 91%* reductions in [α 32 P]UTP incorporation, similar to pretreatment with the RNA polymerase II inhibitor α-amanitin.   Conclusions:  Ang-II regulates gene expression in cardiac FBs through activation of nuclear AT1 and AT2 receptors, with IP3R activation and NO generation being respective effectors. FB nuclear ATR-signaling may regulate FB phenotype and play an important role in cardiac fibrosis and remodeling.
High levels of Gs alpha in platelets of euthymic patients with bipolar affective disorder
Authors: P B Mitchell, H K Manji, G Chen, L Jolkovsky, E Smith-Jackson, K Denicoff, M Schmidt, W Z Potter
Journal: American Journal of Psychiatry (1997)

Previous investigations have suggested the involvement of signal-transducing guanine-nucleotide-binding proteins (G proteins) both in the mechanism of action of lithium and in the pathophysiology of bipolar affective disorder. To determine whether such G protein abnormalities are a trait phenomenon, the authors investigated the levels of G protein alpha subunits in platelets and lymphocytes of euthymic patients with bipolar affective disorder.Selective antibodies were used to quantitate levels of G protein alpha subunits regulating adenylylcyclase activity (Gs alpha-both 45- and 52-kDa forms- and Gil-2 alpha) and those regulating phosphoinositide turnover (Gq/11 alpha) in both platelets and lymphocytes of 44 euthymic patients with bipolar affective disorder and 27 matched comparison subjects.Levels of both Gs alpha 45 and Gs alpha 52 were higher in the platelets of the euthymic bipolar patients (both bipolar I and bipolar II) than in those of the comparison subjects.These findings are consistent with previous reports of high Gs alpha levels in bipolar affective disorder and, furthermore, suggest that such levels may be a trait abnormality for this condition.
EUCAST Definitive Document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts
Authors: J.L. Rodriguez-Tudela, M.C. Arendrup, F. Barchiesi, J. Bille, E. Chryssanthou, M. Cuenca-Estrella, E. Dannaoui, D.W. Denning, J.P. Donnelly, F. Dromer, W. Fegeler, C. Lass-Flörl, C. Moore, M. Richardson, P. Sandven, A. Velegraki, P. Verweij
Journal: Clinical Microbiology and Infection (2008)
Human T-Cell Leukemia Virus Type II Directly Acts on CD34+ Hematopoietic Precursors by Increasing Their Survival Potential. Envelope-Associated HLA Class II Molecules Reverse This Effect
Authors: Claudio Casoli, Maria Carla Re, Paola Monari, Giuliano Furlini, Giovanna Tosi, Chiara Gradozzi, Pier Paolo Dall'Aglio, Umberto Bertazzoni, Roberto S. Accolla
Journal: Blood (1998)
Abstract 13554: Impaired Functional Capacity in Patients With Obstructive Sleep Apnea Predicts Mortality
Authors: Shiraz Nisar, Raghunandan Muppidi, Sumit Duggal, Naveed Iqbal, Adrian Hernandez, Vidyasagar Kalahasti, Wael Jaber, Omar Minai
Journal: Circulation (2011)
Abstract 1171: IQGAP1 Promotes ROS-dependent PDGF Receptor Signaling From Caveolae/lipid rafts to Focal Adhesions: Role in Vascular Migration
Authors: Hyoe Inomata, Minako Yamaoka-Tojo, Norifumi Urao, Taiki Tojo, Ronald Mckinney, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation (2007)
Noninvasive detection and evaluation of atherosclerotic coronary plaques with multislice computed tomography11This study was performed without additional financial support.
Authors: Stephen Schroeder, Andreas F Kopp, Andreas Baumbach, Christoph Meisner, Axel Kuettner, Christian Georg, Bernd Ohnesorge, Christian Herdeg, Claus D Claussen, Karl R Karsch
Journal: Journal of the American College of Cardiology (2001)
Functional Profile of the Isolated Uremic Nephron
Authors: Leon G. Fine, Walter Trizna, Jacques J. Bourgoignie, Neal S. Bricker
Journal: Journal of Clinical Investigation (1978)

An in vitro approach to the study of single nephron function in uremia has been employed in evaluating the control of fluid reabsorption by the renal superficial proximal straight tubule (PST). Isolated segments of PSTs from the remnant kidneys of uremic rabbits (stage III) were perfused in vitro and their rate of fluid reabsorption compared with normal PSTs and with PSTs derived from the remnant kidneys of nonuremic rabbits (stage II). All segments were exposed to a peritubular bathing medium of both normal and uremic rabbit serum thereby permitting a differentiation to be made between adaptations in function which are intrinsic to the tubular epithelium and those which are dependent upon a uremic milieu.
Level of Protein Intake and Nitrogen Excretion in Rats Following Total-Body X Irradiation
Authors: Julius White, Bernard E. Burr, Harriett T. Cool, Philip W. David, Mona S. Ally
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article Level of Protein Intake and Nitrogen Excretion in Rats Following Total-Body X Irradiation Get access Julius White, Julius White National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernard E. Burr, Bernard E. Burr National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Harriett T. Cool, Harriett T. Cool National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip W. David, Philip W. David National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mona S. Ally Mona S. Ally National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 4, February 1955, Pages 1145–1154, https://doi.org/10.1093/jnci/15.4.1145 Published: 01 February 1955 Article history Received: 25 October 1954 Published: 01 February 1955
Greek Registry Of Essential Thrombocythemia: Baseline Characteristics and Therapeutic Strategy
Authors: Damianos Sotiropoulos, Argiris Symeonidis, Vassilios K Papadopoulos, Panagiotis Tsirigotis, Maria Pagoni, Amalia Vassou, Eleftheria Hatzimichael, Emmanouil Spanoudakis, Ioannis Kotsianidis, Alexandra Kouraklis, Polyxeni Lampropoulou, Maria Kotsopoulou, Aikaterini Megalakaki, Charis Matsouka, Despina Barbarousi, Emmanouil S Papadakis, Aggeliki Vourtsi, Anastasia Pouli, Anastasia Sioni, Maria Protopapa, Aikaterini Bitzioni, Anna Pidagitou, Maria Dimou, Dimitris Tsokanas, Anthoula Bouchla, Chrysa Apostolou, Efthimia Vlachaki, Christos Georgopoulos, Nikolaos Anagnostopoulos, Evangelos Briasoulis, Achilles Anagnostopoulos, Panayiotis Panayiotidis, Theodoros Marinakis
Journal: Blood (2013)
Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells
Authors: Hai Wang, Pranay Agarwal, Shuting Zhao, Ronald X. Xu, Jianhua Yu, Xiongbin Lu, Xiaoming He
Journal: Biomaterials (2015)
Abstract 11382: The Efficacy and Safety of Low-Dose Rivaroxaban With or Without a Proton Pump Inhibitor: Insights From the ATLAS ACS 2-TIMI 51 Trial
Authors: Michelle L O’Donoghue, Jessica L Mega, Eugene Braunwald, Jose C Nicolau, Deepak L Bhatt, Sabina A Murphy, C. Michael Gibson
Journal: Circulation (2013)

Background: Omeprazole and esomeprazole can attenuate the pharmacodynamic effects of clopidogrel, although the clinical implications remain unclear. In ATLAS ACS 2-TIMI 52, rivaroxaban (RIVA) reduc...
Abstract 16413: Results of Treadmill Stress Testing Need Not be Interpreted Differently for Predicting Mortality in Obese Patients
Authors: Muaz Abudiab, Bilal Aijaz, Tomas Konecny, Stephen L Kopecky, Ray W Squires, Randal J Thomas, Thomas G Allison
Journal: Circulation (2010)

Background: Reduced functional aerobic capacity (FAC) as measured by treadmill stress testing predicts mortality in normal weight persons. The relationship between FAC and mortality in the obese, however, is unclear. We assessed the hypothesis that obese patients compared to their non-obese counterparts require a more liberal cutoff for FAC for accurate prognostication of mortality. Methods: 5328 non-smoking men (average age, 51.8 ± 11.5 years) without baseline cardiovascular disease referred for treadmill exercise testing during 1986–1991 were classified by body mass index (BMI) into normal weight (18.5–24.9), overweight (25.0–29.9), and obese (30 kg/m2) categories. BMI groups were adjusted for inconsistency with body fat measurements. FAC was assessed by maximal exercise test based on age and gender specific metabolic equivalents (METs), and patients were stratified into fitness quintiles. Cox proportional hazards analysis was used to determine the relationship of all-cause mortality to fitness in each ...
Autophagy Is Required For Long-Term Hematopoietic Stem Cell (HSC) Function and G-CSF-Induced HSC Mobilization
Authors: Lucie Leveque, Therese Vu, Rachel D Kuns, Bianca E Teal, Mary Lor, Katie E Lineburg, Claudia Bruedigam, Frederik Otzen Bagger, Glen Boyle, Geoffrey R Hill, Kelli P A MacDonald, Steven W Lane
Journal: Blood (2013)
CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation
Authors: Ingrid Kuehnle, M. Helen Huls, Zhensheng Liu, Micah Semmelmann, Robert A. Krance, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop
Journal: Blood (2000)
Abstract 3881: Simvastatin versus Therapeutic Lifestyle Changes and Supplements: A Randomized Primary Prevention Trial
Authors: David Becker, Ram Gordon, Patti Morris, Ray Rodriguez, Joseph Pigeon, Nayyar Iqbal
Journal: Circulation (2006)

The primary goal of this study is to examine an alternative treatment (AT) for hyperlipidemia in a primary prevention population by comparing it to established therapy with simvastatin (S). This st...
Smooth pursuit eye movements and saccadic eye movements in patients with delusional disorder
Authors: O Gambini, C Colombo, R Cavallaro, S Scarone
Journal: American Journal of Psychiatry (1993)

This study used eye movement tests to examine whether frontal lobe dysfunction is present in delusional disorder.Smooth pursuit and voluntary saccadic eye movements of 15 delusional patients, 40 schizophrenic patients, and 40 normal subjects were recorded and analyzed statistically.The schizophrenic patients differed significantly from the normal subjects in some smooth pursuit eye movement characteristics, whereas both the schizophrenic and the delusional patients showed more saccades than the normal subjects during the smooth pursuit test. The delusional patients and normal subjects differed significantly in some voluntary saccadic eye movement characteristics.The data support the idea of a biological dysfunction in eye tracking in delusional disorder.
Sensitivity to 35% CO2 in healthy first-degree relatives of patients with panic disorder
Authors: G Perna, S Cocchi, A Bertani, C Arancio, L Bellodi
Journal: American Journal of Psychiatry (1995)

The authors tested the hypothesis that hyperreactivity to CO2 in healthy subjects represents an underlying familial vulnerability to panic disorder.One vital-capacity inhalation of 35% CO2 and 65% O2 was administered to each of 84 patients with panic disorder, 23 healthy first-degree relatives of probands with panic disorder, and 44 healthy subjects with no family history of panic disorder.The first-degree relatives of the probands with panic disorder reacted significantly more than the healthy subjects and significantly less than the probands.These findings suggest an association between family history of panic disorder and hyperreactivity to 35% CO2 in healthy subjects.
Abstract 5822: Interaction Between Acute Kidney Injury and Left Ventricular Remodeling After Myocardial Infarction: Possible Role of Inflammation, Oxidative Stress and Neurohormonal Activation
Authors: Atsushi Anzai, Toshihisa Anzai, Kotaro Naito, Toshiyuki Nagai, Hidehiro Kaneko, Yoshinori Mano, Yuji Nagatomo, Yuichiro Maekawa, Tsutomu Yoshikawa, Satoshi Ogawa
Journal: Circulation (2009)
Abstract 10742: The Common 4q25 Risk Variant for Atrial Fibrillation Interacts with a Variant in the G Protein, Beta Polypeptide 3 Gene (GNB3) to Modify the Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)
Authors: Lin Y Chen, Wei Pan, Alvaro Alonso, Dan E Arking, Kathleen F Kerr, Nona Sotoodehnia, Susan R Heckbert
Journal: Circulation (2012)

Background  Gene-gene interactions in disease can be identified by considering interactions between common risk variants identified from genome-wide association studies and risk variants identified from linkage or candidate gene association studies. We hypothesized that the common 4q25 risk variant for atrial fibrillation (AF), rs2200733 interacts with known risk variants from linkage and association studies to modify the risk of AF. We tested our hypothesis in the Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS).   Methods  We included 9,523 and 3,941 white participants from ARIC and CHS, respectively, who were genotyped using the IBC array-a cardiovascular gene-centric array. We analyzed 431 SNPs in 23 genes ( AGT, AGTR1, ACE, SCN5A ,  KCNQ1 ,  KCNE1 ,  KCNE2 ,  KCNE4 ,  KCNH2,  KCNJ2 ,  KCNA5 ,  ABCC9 ,  GJA5 ,  EMD ,  NPPA ,  LMNA ,  GNB3 ,  SLN ,  SCN2B ,  NOS3 ,  MMP2,   IL10, and PITX2 ). These genes were selected from linkage and association studies for AF. Assuming an additive model, Cox proportional hazards models including an interaction term rs2200733*SNP were used to assess SNP*SNP interaction in relation to incident AF. β coefficients of interaction terms in ARIC and CHS were meta-analyzed. Significance threshold was defined as  P  -4  which corresponds to Bonferroni correction of 312 tests, accounting for SNPs in linkage disequilibrium.   Results  During follow-up, there were 820 and 917 incident AF cases, in ARIC and CHS, respectively. We found a significant interaction between rs2200733 and rs5446 (ARIC: β=0.277, SE=0.101, P=0.006; CHS: β=0.252, SE=0.097, P=0.01; meta-analyzed  P =1.6x10 -4 ). The presence of minor alleles for both rs2200733 and rs5446 increases the risk of AF beyond that is expected from the product of the main effects (Table 1A & 1B).   Conclusions  The common AF risk variant, rs2200733 may interact with rs5446 in G protein, beta polypeptide 3 gene ( GNB3)  to modify the risk of AF. These findings will need to be replicated in other cohorts.
The epidermal growth factor-receptor inhibitor PD153035 upregulates retinoic acid receptor-beta by epigenetic mechanisms
Authors: Thomas W. Grunt, Katharina Tomek, Klaudia Puckmair, Birgit Kainz, Alexander Gaiger, Christoph C. Zielinski
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1248 

Inhibiting epidermal growth factor-receptor (EGFR/ErbB-1) represents a powerful anticancer strategy. Activation of retinoid pathways is also in development for cancer teatment. Retinoic acid receptor-beta (RAR-β) - the tumor suppressor and main retinoid mediator - is silenced in many tumors, but can be reinduced by chromatin-modifying compounds. We and others demonstrated that ErbB and retinoid receptors interact at multiple levels. The EGFR-inhibitor PD153035 cooperates with retinoic acid during growth inhibition and induces RAR-β suggesting that EGFR controls RAR-β. However, here we demonstrate that EGFR is not involved in PD153035-mediated RAR-β-upregulation. PD153035 inhibits EGFR-phosphorylation, whereas its derivative EBE-A22 is inactive. Yet both inhibit cell growth and upregulate RAR-β in EGFR-overexpressing (MDA-MB-468), moderately expressing (OVCAR-3), EGFR-negative (MDA-MB-453) or ErbB-negative cells (CEM, Jurkat). No other EGFR/ErbB-2 inhibitor (ZD1839, RG-14620, LFM-A12, AG879, AG825) affects RAR-β. PD153035-mediated upregulation is specific for RAR-β: No other retinoid receptor, nor estrogen receptor-α, nor tumor suppressor RASSF1A is upregulated by PD153035. PD153035 causes demethylation of RAR-β2 promoter. This might be related to DNA-intercalating activity of PD153035. In OVCAR-3, PD153035 stimulates H3/H4 histone acetylation at RAR-β promoter. Thus PD153035 induces RAR-β by EGFR-independent mechanisms. This report highlights a triple action for an EGFR inhibitor (EGFR-inhibition, DNA-intercalation, epigenetic RAR-β-induction). Such multitargeting drugs bear great potential for cancer treatment.
Abstract 20035: Purinergic Endothelium Independent Vasodilation: The Role of Protein Kinase C and Two-Pore Domain Potassium Channels
Authors: Sebastien Hayoz, Luis Cubano, Hector Maldonado, Rostislav Bychkov
Journal: Circulation (2010)

Background:  K +  channels family identified as “two-pore K + - channels (K2P)” function as leak K +  efflux. K2P channels have been reported in pulmonary arteries and mesenteric beds. Which intracellular cascades regulate opening of K2P-channels in thoracic aorta? Could the opening of leak-current impact vasodilation?   Methods and results:  Patch-clamp technique was used to record ATPγs-elicited currents in freshly dissociated myocytes. ATPγs elicited bi-phasic response. First ATPγs stimulated burst of Cl-current spikes coupled to Ca 2+  oscillations. Then, ATPγs increased amplitude of outward net K + -current. This current was resistive to K +  channels blockers (TEA, 4AP, charibdotoxin, apamin, and glibenclamide). Tested purinergic agonists (ATP, UTP) — except for ADP — activated, delayed K + -current indicating that at least P2Y11 receptor stimulates delayed K + -current. ATPγs increased amplitude of K +  blockers resistive current in 8BrcAMP pretreated cells. PKC agonist (4α-phorbol-12,13-didecanoate) increased amplitude of K +  blockers resistive current. ATPγs added cumulatively to PKC agonist did not further increase the amplitude of the outward net current. ATPγs-elicited K + -current amplitude decreased in staurosporine and G6850 pretreated cells. Acid pH (pH=6) inhibited when basic pH (pH=8) stimulated amplitude of ATPγs-elicited K + -current. ATPγs produced a vasodilation in endothelium-denuded thoracic aorta rings, contracted by the K + -channels blockers and pre-treated by carbenoxolone. PKC agonist mimicked ATPγs-elicited vasodilation.   Conclusions:  Our results demonstrate that ATPγs opens K2P-channels via activation of PKC and dilates pre-stretched thoracic aorta rings. Taken together, our data provides new cellular mechanism of vasoregulation in conduit arteries.
Cardiovascular risk scores and prescribing in diabetes
Authors: J. Smith
Journal: BMJ (2003)

Editor—Hall et al describe the use of primary prevention risk tables in type 2 diabetes.1 We agree that targeting cardiovascular risk in diabetes is a priority, but their proposals imply an overreliance on risk scores as the sole determinant of cardiovascular risk assessment in diabetes. This approach might lead to withholding treatment in some people whose risk is underestimated by risk scores.

Unfortunately, the decision at what level of cardiovascular risk to start lipid lowering treatment in diabetes is not straightforward. The authors' oversimplistic approach, although convenient, is unscientific and flies in the face of epidemiological evidence which suggests that type 2 diabetes should be regarded as a disease group for secondary rather than primary prevention.2

Using the Framingham equation to evaluate cardiovascular risk in diabetes entails caveats. These include a low baseline prevalence of diabetes in the Framingham cohort and the omission from the equation of triglyceride concentration, an important determinant of cardiovascular risk in type 2 diabetes.3 The low prevalence of diabetes in the cohort leads to wide confidence intervals in the predicted risk. Thus, in a diabetic man with average risk factors, the upper 95% confidence interval crosses the 15%, 10 year threshold from the age of 40 onwards.3

People with risk scores below a chosen cut-off point may therefore have a higher true risk. The proposals by Hall et al would lead to a rigid prescribing protocol whereby all patients with scores above a threshold (for example, 15%) would receive treatment, whereas those below would not. Furthermore, an overemphasis on the risk score might be at the expense of ignoring other key factors not represented by the Framingham risk equation, such as ethnic group, family history, microalbuminuria, and triglyceride concentration.
Abstract 3993: The BH3-only Protein Bnip3 Mediates Mitochondrial Autophagy via Recruitment of the Ubiquitin Ligase Parkin
Authors: Youngil Lee, Melissa N Quinsay, Sivaji Rikka, Chenqun Huang, Asa B Gustafsson
Journal: Circulation (2009)

Bnip3 is a pro-apoptotic BH3-only protein which is associated with mitochondrial dysfunction and cell death in the heart. Bnip3 has also been shown to induce autophagy in many cells. Here, we investigated whether Bnip3 induced autophagy in primary adult cardiac myocytes by utilizing adenoviral infections of cells coupled with fluorescence deconvolution microscopy. Imaging of myocytes infected with adenoviruses expressing GFP-LC3 and Bnip3 or beta-gal were used to monitor formation of autophagosomes in cells. Overexpression of Bnip3 induced rapid increase in autophagy in adult cardiac myocytes (94.0±4.1%; n=3; p