tbuckley/cabot-search huggingface dataset:
Gα <sub>q</sub> and Gβγ Regulate PAR-1 Signaling of Thrombin-Induced NF-κB Activation and ICAM-1 Transcription in Endothelial Cells
Authors: Arshad Rahman, Andrea L. True, Khandaker N. Anwar, Richard D. Ye, Tatyana A. Voyno-Yasenetskaya, Asrar B. Malik
Journal: Circulation Research (2002)

As thrombin binding to the G protein–coupled proteinase activated receptor-1 (PAR-1) induces endothelial adhesivity to leukocytes through NF-κB activation and intercellular adhesion molecule-1 (ICAM-1) expression, we determined the signaling pathways mediating the response. Studies showed that the heterotrimeric G proteins, Gα q , and the Gβγ dimer were key determinants of the PAR-1 agonist peptide (TFLLRNPNDK)-induced NF-κB activation and ICAM-1 expression in endothelial cells. Cotransfection of RGS3T, a regulator of G-protein signaling that inhibits Gα q , or α-transducin (Gα t ), a scavenger of the Gβγ, markedly decreased NF-κB activity induced by PAR-1 activation. We determined the downstream signaling targets activated by Gα q and Gβγ that mediate NF-κB activation. Expression of the kinase-defective protein kinase C (PKC)-δ mutant inhibited NF-κB activation induced by the constitutively active Gα q mutant, but had no effect on NF-κB activity induced by Gβ 1 γ 2 . In related experiments, NF-κB as well as ICAM-1 promoter activation induced by Gβ 1 γ 2 were inhibited by the expression of the dominant-negative mutant of 85-kDa regulatory subunit of PI 3-kinase; however, the expression of this mutant had no effect on the response induced by activated Gα q . Cotransfection of the catalytically inactive Akt mutant inhibited the NF-κB activation induced by the constitutively active PI 3-kinase mutant as well as that by the activated forms of Gα q and PKC-δ. These results support a model in which ligation of PAR-1 induces NF-κB activation and ICAM-1 transcription by the engagement of parallel Gαq/PKC-δ and Gβγ/PI3-kinase pathways that converge at Akt.
Survival Benefit With Radium-223 Dichloride in a Mouse Model of Breast Cancer Bone Metastasis
Authors: Mari I. Suominen, Jukka P. Rissanen, Rami Käkönen, Katja M. Fagerlund, Esa Alhoniemi, Dominik Mumberg, Karl Ziegelbauer, Jussi M. Halleen, Sanna-Maria Käkönen, Arne Scholz
Journal: JNCI Journal of the National Cancer Institute (2013)

BackgroundBone metastases are associated with increased morbidity and poor prognosis in breast cancer patients. Radium-223 dichloride is a calcium mimetic that localizes to bone, providing targeted therapy for skeletal metastasis.
Noninvasive diagnosis of physiologic stenosis in the left circumflex coronary artery using contrast enhanced transthoracic Doppler echocardiography: comparison with exercise 201-TI Single Photon Emission Computed Tomography
Authors: Kotaro Tokai, Hiroyuki Watanabe, Hiroyuki Yamagishi, Kumiko Hirata, Ryo Otsuka, Takashi Muro, Minoru Yoshiyama, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2002)
Death Patterns in Sickle Cell Anemia
Authors: Edward 'B. Attah
Journal: JAMA (1975)

In Ibadan, Nigeria, 28 patients with sickle cell disease (hemoglobin SS and SC) died and were autopsied. Fifty percent of these had died by the age of 5 years, as did 21 (68%) with homozygous hemoglobin SS disease. No death occurred in infancy or childhood among the patients with hemoglobin SC disease. Serious intercurrent disease that could have been responsible for death was present in ten patients (36%). The type and frequency of intercurrent disease appears to be related to the environment. (<i>JAMA</i>233:889-890, 1975)
Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review
Authors: A. J M de Craen, G. Di Giulio, A. J E M Lampe-Schoenmaeckers, A. G H Kessels, J. Kleijnen
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To assess whether adding codeine to paracetamol has an additive analgesic effect; to assess the safety of paracetamol-codeine combinations versus paracetamol alone. <b>Design</b>: Systematic literature review with meta-analysis, methodological quality of published trials being scored by means of 13 predefined criteria. <b>Trials</b>: 24 of 29 trials that met the inclusion criteria. Models studied in the trials were postsurgical pain (21), postpartum pain (one), osteoarthritic pain (one), and experimentally induced pain (one). <b>Interventions</b>: Dosages ranged from 400 to 1000 mg paracetamol and 10 to 60 mg codeine. <b>Main outcome measures</b>: The sum pain intensity difference (efficacy analysis)and the proportion of patients reporting a side effect (safety analysis). <b>Results</b>: Most trials were considered of good to very good quality. Only the single dose studies could be combined for analysis of analgesic efficacy. Pooled efficacy results indicated that codeine added to paracetamol provided a 5% increase in analgesia on the sum pain intensity difference. This effect was comparable to the difference in analgesic effect between codeine and placebo. The cumulative incidence of side effects with each treatment was comparable in the single dose trials. In the multidose studies a significantly higher proportion of side effects occurred with paracetamol-codeine preparations. <b>Conclusion</b>: The difference in analgesic effect between paracetamol-codeine combinations and paracetamol alone was small but statistically significant. In the multidose studies the proportion of patients reporting a side effect was significantly higher with paracetamol-codeine combinations. For occasional pain relief a paracetamol-codeine combination might be appropriate but repeated use increases the occurrence of side effects. <h3>Key messages</h3> Paracetamol-codeine combinations are thought to bring more pain relief than that achieved with paracetamol alone Single dose studies show a slightly increased analgesic effect when codeine is added to paraceta- mol In single dosage the incidence of side effects with paracetamol alone and paracetamol plus codeine is similar; in multidosage side effects are significantly increased with paracetamol-codeine preparations A paracetamol-codeine preparation is recom- mended when more pain relief is needed with a single dose of a drug; more side effects may occur with multiple dosage
Hypoxia-Driven Gene Expression Is an Independent Prognostic Factor in Stage II and III Colon Cancer Patients
Authors: Jeroen Dekervel, Daphne Hompes, Hannah van Malenstein, Dusan Popovic, Xavier Sagaert, Bart De Moor, Eric Van Cutsem, André D'Hoore, Chris Verslype, Jos van Pelt
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients. Experimental Design: Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray datasets. These datasets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin-embedded material of 126 patients with colon cancer treated in our center. Results: In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected P ≤ 0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n = 224). With a fourth published dataset (n = 177), the six-gene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease-free survival at three years (77.3%) compared with high CCHS patients (46.4%; log-rank, P = 0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs. 52.2%; P = 0.001). Conclusions: Hypoxia-driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A six-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledge on molecular classification of colon cancer. Clin Cancer Res; 20(8); 2159–68. ©2014 AACR.
The <scp>CC</scp> genotype of the <i> <scp>ERCC</scp> 1 </i> C118T single‐nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo
Authors: E.H. Kemp
Journal: British Journal of Dermatology (2015)

This is a repository copy of The CC genotype of the ERCC1 C118T single-nucleotide polymorphism impacts positively on the efficacy of narrowband ultraviolet B therapy for vitiligo..
Effect of chronic and acute cigarette smoking on the pharyngoglottal closure reflex
Authors: K Dua
Journal: Gut (2002)

<b>Background:</b> Injection of water into the pharynx at a threshold volume induces vocal cord adduction—the pharyngoglottal closure reflex (PGCR). This reflex together with other supraoesophageal reflexes may be helpful in preventing aspiration. Cigarette smoking has an adverse affect on the pharyngo-upper oesophageal sphincter contractile reflex and reflexive pharyngeal swallow. The effect of smoking on PGCR has not been studied previously. <b>Aims:</b> To elucidate the effect of chronic and acute cigarette smoking on PGCR. <b>Subjects:</b> We studied 10 chronic smokers and 10 non-smokers before and after real/simulated smoking, respectively. <b>Methods:</b> Using concurrent recordings, glottal function was monitored by video endoscopy, swallowing by electromyography, and PGCR was triggered by rapid and slow pharyngeal water injections. <b>Results:</b> The threshold volume to trigger PGCR during rapid injection was significantly higher in chronic smokers (non-smoker 0.20 (SEM 0.02) ml, smoker 0.36 (0.02) ml; p&lt;0.001). In six of 10 smokers, acute smoking abolished this reflex during slow water injection. <b>Conclusions:</b> Smoking adversely affects stimulation of PGCR. This finding may have implications in the development of reflux related respiratory complications in smokers.
A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer
Authors: J.P. Sculier, J.J. Lafitte, J. Lecomte, T. Berghmans, J. Thiriaux, M.C. Florin, A. Efremidis, C.G. Alexopoulos, P. Recloux, V. Ninane, P. Mommen, M. Paesmans, J. Klastersky
Journal: Annals of Oncology (2002)
Ontogeny of endothelins-1 and -3, their receptors, and endothelin converting enzyme-1 in the early human embryo.
Authors: M Brand, J M Le Moullec, P Corvol, J M Gasc
Journal: Journal of Clinical Investigation (1998)

The targeted gene inactivation of endothelins-1 and -3 (ET-1 and ET-3) and of one of their receptors, ETB, in the mouse causes severe defects in the embryonic development. These defects, cardiovascular and craniofacial malformations for ET-1, and colonic agangliogenesis associated with skin pigmentation anomalies for ET-3 and the ETB receptor, reproduce pathological phenotypes due to natural mutations of the same genes in the mouse and the human. The mutant phenotypes have been causatively linked to deficient migration/proliferation/differentiation of neural crest cells, i.e., neurocristopathies. To bring new insight about the exact roles of ETs in development and the involvement of neural crest cells in these processes, we have explored, by in situ hybridization, the ontogeny in the early human embryo of the ET system (ET-1 and ET-3, ETA and ETB receptors, ET converting enzyme-1). ET receptor mRNA expression in neural crest cells starts at 3 wk of gestation and continues during the entire period studied (up to 6 wk of gestation). During this period, ETA expression progressively spreads to undifferentiated mesodermal components of various structures and organs (head and axial skeleton, lateral and ventral subdermal mesoderm), whereas ETB expression remains more restricted to fewer differentiated cells (neural tube, sensory and sympathetic ganglia, endothelium). Some of these tissues and structures that express either one of the receptors do not appear to be of neural crest origin. In the digestive tract and the cardiovascular area, the present observations on the sources of ETs and their target cells in the young embryo provide the basis for a dynamic interpretation of the results of gene targeting of the mouse and the human phenotypes, and point to other possible roles of ETs in other ontogenetic processes. The results support the concept of local, rather than hormonal, interactions between the sources and targets of ETs during development.
Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains
Authors: Matthew C. Pickering, Elena Goicoechea de Jorge, Rubén Martinez-Barricarte, Sergio Recalde, Alfredo Garcia-Layana, Kirsten L. Rose, Jill Moss, Mark J. Walport, H. Terence Cook, Santiago Rodriguez de Córdoba, Marina Botto
Journal: The Journal of Experimental Medicine (2007)

Factor H (FH) is an abundant serum glycoprotein that regulates the alternative pathway of complement-preventing uncontrolled plasma C3 activation and nonspecific damage to host tissues. Age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and membranoproliferative glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations in the FH gene (Cfh), suggesting the existence of a genotype–phenotype relationship. Although AMD and MPGN2 share pathological similarities with the accumulation of complement-containing debris within the eye and kidney, respectively, aHUS is characterized by renal endothelial injury. This pathological distinction was reflected in our Cfh association analysis, which demonstrated that although AMD and MPGN2 share a Cfh at-risk haplotype, the haplotype for aHUS was unique. FH-deficient mice have uncontrolled plasma C3 activation and spontaneously develop MPGN2 but not aHUS. We show that these mice, transgenically expressing a mouse FH protein functionally equivalent to aHUS-associated human FH mutants, regulate C3 activation in plasma and spontaneously develop aHUS but not MPGN2. These animals represent the first model of aHUS and provide in vivo evidence that effective plasma C3 regulation and the defective control of complement activation on renal endothelium are the critical events in the molecular pathogenesis of FH-associated aHUS.
Sarcoidosis from bench to bedside: a state-of-the-art series for the clinician
Authors: Vincent Cottin, Joachim Müller-Quernheim
Journal: European Respiratory Journal (2012)

First described in 1899 [1], sarcoidosis is a multi-organ granulomatous disorder that remains an enigma and challenges researchers and clinicians due to its unknown aetiology, variegated presentation and an unpredictable, and occasionally severe or even fatal, outcome despite therapy. As over 90% of patients have involvement of the lungs and thoracic lymph nodes, most chest physicians encounter sarcoidosis regularly in their practice, and have to manage this disorder with a risk of delayed or inadequate care [1].

Sarcoidosis may cause significant morbidity, as it persists as a chronic disease in approximately one-third of cases [1]. It most commonly affects individuals aged 20–39 yrs [2]. The prevalence of disease varies widely throughout the world and in ethnic groups, with a mean estimate of 15 cases per 100,000 persons, roughly corresponding to one in 6,000 persons in the general population [3]. In Ireland, England, central Europe and Scandinavia the prevalence ranges between 40 and 60 cases per 100,000 and associations with environmental and occupational exposure have been reported [4–8].

In the past, the European Respiratory Journal ( ERJ ) has disseminated advances in knowledge of sarcoidosis and is committed to doing so consistently. To this end, the ERJ has, in the June issue, started a new series on sarcoidosis that will provide an in-depth overview of the tremendous progress made in this field in recent years. This series of articles intends to provide readers with the most up-to-date and comprehensive reviews. The authors are among the world’s leading experts in the field of sarcoidosis, and the articles are intended to be practically oriented and relevant for practicing physicians without neglecting the cutting edge of research. Topics developed in the series were carefully chosen as those with …
Ferric Gluconate Reduces Epoetin Requirements in Hemodialysis Patients with Elevated Ferritin
Authors: Toros Kapoian, Neeta B. O'Mara, Ajay K. Singh, John Moran, Adel R. Rizkala, Robert Geronemus, Robert C. Kopelman, Naomi V. Dahl, Daniel W. Coyne
Journal: Journal of the American Society of Nephrology (2008)

The Dialysis Patients Response to IV Iron with Elevated Ferritin (DRIVE) study demonstrated the efficacy of intravenous ferric gluconate to improve hemoglobin levels in anemic hemodialysis patients who were receiving adequate epoetin doses and who had ferritin levels between 500 and 1200 ng/ml and transferrin saturation (TSAT) < or = 25%. The DRIVE-II study reported here was a 6-wk observational extension designed to investigate how ferric gluconate impacted epoetin dosage after DRIVE. During DRIVE-II, treating nephrologists and anemia managers adjusted doses of epoetin and intravenous iron as clinically indicated. By the end of observation, patients in the ferric gluconate group required significantly less epoetin than their DRIVE dose (mean change of -7527 +/- 18,021 IU/wk, P = 0.003), whereas the epoetin dose essentially did not change for patients in the control group (mean change of 649 +/- 19,987 IU/wk, P = 0.809). Mean hemoglobin, TSAT, and serum ferritin levels remained higher in the ferric gluconate group than in the control group (P = 0.062, P < 0.001, and P = 0.014, respectively). Over the entire 12-wk study period (DRIVE plus DRIVE-II), the control group experienced significantly more serious adverse events than the ferric gluconate group (incidence rate ratio = 1.73, P = 0.041). In conclusion, ferric gluconate maintains hemoglobin and allows lower epoetin doses in anemic hemodialysis patients with low TSAT and ferritin levels up to 1200 ng/ml.
Membrane Potential Fluctuations Resulting From Submembrane Ca <sup>2+</sup> Releases in Rabbit Sinoatrial Nodal Cells Impart an Exponential Phase to the Late Diastolic Depolarization That Controls Their Chronotropic State
Authors: Konstantin Y. Bogdanov, Victor A. Maltsev, Tatiana M. Vinogradova, Alexey E. Lyashkov, Harold A. Spurgeon, Michael D. Stern, Edward G. Lakatta
Journal: Circulation Research (2006)

Stochastic but roughly periodic LCRs ( L ocal subsarcolemmal ryanodine receptor–mediated C a 2+ R eleases) during the late phase of diastolic depolarization (DD) in rabbit sinoatrial nodal pacemaker cells (SANCs) generate an inward current ( I NCX ) via the Na + /Ca 2+ exchanger. Although LCR characteristics have been correlated with spontaneous beating, the specific link between LCR characteristics and SANC spontaneous beating rate, ie, impact of LCRs on the fine structure of the DD, have not been explicitly defined. Here we determined how LCRs and resultant I NCX impact on the DD fine structure to control the spontaneous SANC firing rate. Membrane potential ( V m ) recordings combined with confocal Ca 2+ measurements showed that LCRs impart a nonlinear, exponentially rising phase to the DD later part, which exhibited beat-to-beat V m fluctuations with an amplitude of approximately 2 mV. Maneuvers that altered LCR timing or amplitude of the nonlinear DD (ryanodine, BAPTA, nifedipine or isoproterenol) produced corresponding changes in V m fluctuations during the nonlinear DD component, and the V m fluctuation response evoked by these maneuvers was tightly correlated with the concurrent changes in spontaneous beating rate induced by these perturbations. Numerical modeling, using measured LCR characteristics under these perturbations, predicted a family of local I NCX that reproduced V m fluctuations measured experimentally and determined the onset and amplitude of the nonlinear DD component and the beating rate. Thus, beat-to-beat V m fluctuations during late DD phase reflect the underlying LCR/ I NCX events, and the ensemble of these events forms the nonlinear DD component that ultimately controls the SANC chronotropic state in tight cooperation with surface membrane ion channels.
Comparison of repolarization and inflammatory activity in patients with and without ventricular fibrillation during acute myocardial infarction of a similar size (CK &lt; 1000 U/I)
Authors: Ayse Bilbal, Susanne Spehl, Constanze Echternach, Jürgen Kuschyk, Florian Streitner, Stefan Pfleger, Tim Süselbeck, Karl K. Haase, Martin Borggrefe, Christian Wolpert
Journal: Journal of the American College of Cardiology (2003)
THE USE OF GROUP PROCESSES IN TEACHING GROUP DYNAMICS
Authors: ELVIN V. SEMRAD, JOHN ARSENIAN
Journal: American Journal of Psychiatry (1951)

A method of teaching group dynamics by forming groups is described and some of our experience with it detailed. In evaluating the experience, the opinions of participants vary widely but most report that they have learned something and may have carried over their newly formulated experience into other groups. The bridge between theory and practice is readily crossed by this method of teaching and many people come away with new insights into how to observe and/or conduct both themselves and group meetings more effectively.
Relation between respiratory symptoms, pulmonary function and peak flow variability in adults.
Authors: H M Boezen, J P Schouten, D S Postma, B Rijcken
Journal: Thorax (1995)

BACKGROUND--A study was carried out to determine whether subjects with respiratory symptoms are more likely to have impaired lung function or increased airway lability, and to quantify these relationships in a population of adults. METHODS--Data were collected from 511 participants (aged 20-70 years) from the Dutch part of the European Community Respiratory Health Survey (ECRHS). The symptoms analysed were: wheeze, dyspnoea &gt; or = grade 3, nocturnal dyspnoea, cough and phlegm, and history of allergy. Lung function was measured by peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). PEF variability was used as an index for bronchial lability. RESULTS--Both FEV1 and PEF were decreased with increasing numbers of symptoms. Subjects with one symptom had an increased risk of having an FEV1 value of &lt; 70% (OR = 4.2) and this risk increased with an increasing number of symptoms. Subjects with three or more symptoms had an increased risk of having a PEF value of &lt; 70%, a diurnal variation in PEF of &gt; 10% (both OR = 4.4), and an increased risk of high between day variation (OR = 6.6). CONCLUSIONS--Subject-reported symptoms are related to impaired lung function and to increased variability of peak flow.