tbuckley/cabot-search huggingface dataset:
Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation
Authors: Anette Varbo, Marianne Benn, Anne Tybjærg-Hansen, Børge G. Nordestgaard
Journal: Circulation (2013)

Background— Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown. Methods and Results— We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by CRP alleles, and C-reactive protein by IL6R alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35–39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10–48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6–7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1–5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5–2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity. Conclusions— Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation.
Factors determining early adherence to a lung cancer screening protocol
Authors: U. Montes, L. M. Seijo, A. Campo, A. B. Alcaide, G. Bastarrika, J. J. Zulueta
Journal: European Respiratory Journal (2007)

Lung cancer screening using computed tomography (CT) is effective in detecting early stage disease. However, concerns regarding adherence have been raised. The current authors conducted a retrospective observational study of 641 asymptomatic smokers enrolled in a lung cancer screening programme between 2000 and 2003. Adherent subjects were compared with nonadherent subjects with regard to lung function, sex, age, motivation for enrollment, smoking status, distance to the referral centre, family history of lung cancer, asbestos exposure, education, the presence and type of nodule(s) seen on initial CT, and exposure to a nursing intervention designed to improve adherence. Overall, early adherence to the study protocol was 65%. Multivariate analysis confirmed the importance of sex, proximity to the referral centre, the presence of noncalcified nodules, and the nursing intervention as factors conditioning adherence to the study protocol. Patients encouraged to participate in the study were more adherent, as were former smokers. Sex interactions were observed in multivariate analysis. The nursing intervention was significant for females, while abnormal lung function improved male adherence. Adherence to lung cancer screening is particularly good among females and subjects living near the referral centre. The present study suggests the need to develop new strategies, especially those targeting males and subjects with low risk perception, in order to improve adherence.
Prognostic value of chromosome 1q21 gain by fluorescent in situ hybridization and increase CKS1B expression in myeloma
Authors: R Fonseca, S A Van Wier, W J Chng, R Ketterling, M Q Lacy, A Dispenzieri, P L Bergsagel, S V Rajkumar, P R Greipp, M R Litzow, T Price-Troska, K J Henderson, G J Ahmann, M A Gertz
Journal: Leukemia (2006)
Memory B cell responses following immunisation with polysaccharide and conjugate quadrivalent meningococcal ACYW135 vaccines in healthy adult volunteers
Authors: Maheshi Ramasamy, Elizabeth Clutterbuck, Jaclyn Bowman, Matthew D. Snape, Mushiya Mpelembue, Kathryn Haworth, Andrew J. Pollard
Journal: Journal of Infection (2010)
Emerging translational approaches to target STAT3 signalling and its impact on vascular disease
Authors: Jochen Dutzmann, Jan-Marcus Daniel, Johann Bauersachs, Denise Hilfiker-Kleiner, Daniel G. Sedding
Journal: Cardiovascular Research (2015)

Acute and chronic inflammation responses characterize the vascular remodelling processes in atherosclerosis, restenosis, pulmonary arterial hypertension, and angiogenesis. The functional and phenotypic changes in diverse vascular cell types are mediated by complex signalling cascades that initiate and control genetic reprogramming. The signalling molecule's signal transducer and activator of transcription 3 (STAT3) plays a key role in the initiation and continuation of these pathophysiological changes. This review highlights the pivotal involvement of STAT3 in pathological vascular remodelling processes and discusses potential translational therapies, which target STAT3 signalling, to prevent and treat cardiovascular diseases. Moreover, current clinical trials using highly effective and selective inhibitors of STAT3 signalling for distinct diseases, such as myelofibrosis and rheumatoid arthritis, are discussed with regard to their vascular (side-) effects and their potential to pave the way for a direct use of these molecules for the prevention or treatment of vascular diseases.
Surgery for Primary Cardiac Tumors in Children
Authors: Massimo A. Padalino, Vladimiro L. Vida, Giovanna Boccuzzo, Marco Tonello, George E. Sarris, Hakan Berggren, Juan V. Comas, Duccio Di Carlo, Roberto M. Di Donato, Tjark Ebels, Viktor Hraska, Jeffrey P. Jacobs, J. William Gaynor, Dominique Metras, Rene Pretre, Marco Pozzi, Jean Rubay, Heikki Sairanen, Christian Schreiber, Bohdan Maruszewski, Cristina Basso, Giovanni Stellin
Journal: Circulation (2012)

To evaluate indications and results of surgery for primary cardiac tumors in children.Eighty-nine patients aged ≤18 years undergoing surgery for cardiac tumor between 1990 and 2005 from 16 centers were included retrospectively (M/F=41/48; median age 4.3 months, range 1 day to 18 years). Sixty-three patients (68.5%) presented with symptoms. Surgery consisted of complete resection in 62 (69.7%) patients, partial resection in 21 (23.6%), and cardiac transplant in 4 (4.5%). Most frequent histotypes (93.2%) were benign (rhabdomyoma, myxoma, teratoma, fibroma, and hemangioma). Postoperative complications occurred in 29.9%. Early and late mortality were 4.5% each (mean follow-up, 6.3±4.4 years); major adverse events occurred in 28.2% of the patients; 90.7% of patients are in New York Heart Association class I. There were no statistically significant differences in survival, postoperative complications, or adverse events after complete and partial resection in benign tumors other than myxomas. Cardiac transplant was associated significantly with higher mortality rate (P=0.006). Overall mortality was associated to malignancy (P=0.0008), and adverse events during follow-up (P=0.005).Surgery for primary cardiac tumors in children has good early and long-term outcomes, with low recurrence rate. Rhabdomyomas are the most frequent surgical histotypes. Malignant tumors negatively affect early and late survival. Heart transplant is indicated when conservative surgery is not feasible. Lack of recurrence after partial resection of benign cardiac tumors indicates that a less risky tumor debulking is effective for a subset of histotypes such as rhabdomyomas and fibromas.
Outcome Analyses After the First Admission to an Intensive Care Unit in Patients With Advanced Cancer Referred to a Phase I Clinical Trials Program
Authors: Siqing Fu, David S. Hong, Aung Naing, Jennifer Wheler, Gerald Falchook, Sijin Wen, Adrienne Howard, Diane Barber, Joseph Nates, Kristen Price, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2011)

This study assessed outcomes of individuals with advanced cancer who required admission to an intensive care unit (ICU) after referral for an early clinical trial because they did not respond to conventional therapy.Outcome analyses were conducted for 212 consecutive patients admitted to The University of Texas MD Anderson Cancer Center ICU after being seen in the phase I clinic starting on May 1, 2007. All data were obtained by a review of electronic medical records of patients.The median survival of 212 patients with advanced cancer referred to phase I care after the initial ICU admission was 3.2 weeks (95% CI, 2.5 to 4.9 weeks). Patients who underwent cardiopulmonary resuscitation (CPR) succumbed within a median survival of 1 day (75% and 25% estimated survival of 1 and 3 days, respectively). Patients admitted for a postsurgical intervention did better than patients admitted for a nonsurgical intervention (median survival, 21.5 versus 2.1 weeks; P < .0001). The multivariate analysis revealed that a nonsurgical intervention, hypoalbuminemia, and higher Acute Physiology and Chronic Health Evaluation II scores were associated with poor overall survival.The outcome of patients in a phase I clinic after initial ICU admission was poor, particularly when admission was for a nonsurgical intervention and/or when CPR was needed.
Systemic pyoderma gangrenosum responding to infliximab and adalimumab
Authors: V.G. Hubbard, A.C. Friedmann, P. Goldsmith
Journal: British Journal of Dermatology (2005)

Pyoderma gangrenosum (PG) is frequently associated with constitutional symptoms as part of a nonspecific inflammatory response. However, extracutaneous discrete aseptic neutrophilic infiltrates are extremely rare. We report a patient with idiopathic PG with splenic and psoas muscle involvement. His disease was extremely aggressive and was unresponsive to conventional immunosuppressive therapy. His cutaneous and extracutaneous PG cleared with infliximab and adalimumab.
Lung injury following pulmonary resection in the isolated, blood‐perfused rat lung
Authors: E.A. Williams, G.J. Quinlan, P.b Anning, P Goldstraw, T.W. Evans
Journal: European Respiratory Journal (1999)

Lung resection may be complicated by postpneumonectomy pulmonary oedema. Oxidant generation following surgery-induced ischaemia-reperfusion may be responsible. This hypothesis was tested utilizing isolated, in situ, blood perfused rodent lungs subjected to continuous perfusion (control subjects); one lung ventilation followed by pneumonectomy (group 1); or one lung ventilation followed by reinflation of the collapsed lung (group 2). In control subjects, no significant changes in markers of oxidant damage, oxygenation, pulmonary artery pressure or extravascular albumin extravasation were detected. In group 1 lungs, hydroxyl radical-like damage was detected in association with impaired oxygenation (p&lt;0.05), and increased pulmonary artery pressure and extravascular albumin accumulation in both lungs. In group 2, there was evidence of hydroxyl radical-like damage, and a fall in oxygenation (p&lt;0.05) occurred during one lung ventilation. There was a transient rise in pulmonary artery pressure following lung reinflation and extra vascular albumin accumulation was significantly increased in both lungs (right&gt;left, p&lt;0.05). Both changes were attenuated (p&lt;0.05) following treatment with the reactive oxygen species (ROS) scavenger superoxide dismutase (group 2a) and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (group 2b). Hydroxyl radical-like damage was undetectable following nitric oxide synthase inhibition. Oxidant stress may contribute to the pathologies seen in this model of lung injury.
A Core System for the Implementation of Task Sets
Authors: Nico U.F. Dosenbach, Kristina M. Visscher, Erica D. Palmer, Francis M. Miezin, Kristin K. Wenger, Hyunseon C. Kang, E. Darcy Burgund, Ansley L. Grimes, Bradley L. Schlaggar, Steven E. Petersen
Journal: Neuron (2006)
Comparison of two methods of collecting induced sputum in asthmatic subjects
Authors: NH Gershman, HH Wong, JT Liu, MJ Mahlmeister, JV Fahy
Journal: European Respiratory Journal (1996)

The method that we have previously reported for sputum induction involves collecting the entire expectorate produced over a 20 min inhalation of 3% saline aerosol. This method presents the potential disadvantage of a considerable and variable salivary contribution to the induced sputum sample. In this study, we examined whether separate collection of saliva and sputum represents a better method for collecting induced sputum during sputum induction. In 11 stable asthmatics, we compared the volume, total and differential cell counts, and eosinophil cationic protein (ECP) levels in four induced sputum samples, two performed using our previous method (Method A) and two using another method (Method B) in which subjects spit saliva into one container before coughing sputum into another. We found that the volume of sputum obtained with Method B was lower than that obtained with Method A (6.16 +/- 0.61 vs 20.1 +/- 2.7 mL; p = 0.003), as was the percentage of squamous cells (34 +/- 4 vs 47 +/- 6; p = 0.023). In addition, the ECP levels in samples collected by Method B were higher (261 +/- 42 vs 145 +/- 26 ng.mL-1; p = 0.01). The differential counts of nonsquamous cells were similar except for the percentage of neutrophils, which was lower in Method B (37 +/- 4 vs 50 +/- 5%; p = 0.019). The repeatability of measurements of eosinophil percentages and of ECP levels was similar for the two methods. We conclude that separate collection of saliva and sputum yields induced sputum samples with reduced amounts of saliva and is, therefore, a better method for collecting induced sputum.
Specific Cre/Lox Recombination in the Mouse Proximal Tubule
Authors: Isabelle Rubera, Chantal Poujeol, Guillaume Bertin, Lilia Hasseine, Laurent Counillon, Philippe Poujeol, Michel Tauc
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The present work reports for the first time the construction of a transgenic mouse strain with specific expression of Cre recombinase in the kidney proximal tubule. A Cre/loxP strategy was developed using sglt2 promoter to drive Cre recombinase expression in transgenic mice. The mouse sglt2 5′ region consisting of the first exon, the first intron, and part of the second exon was cloned upstream of a nucleotide sequence encoding the Cre recombinase. Transgenic mice were generated by pronuclear injection, and tissue specificity of Cre expression was analyzed using reverse transcription-PCR. The iL1-sglt2-Cre mouse line scored positive for kidney transcription of Cre but not for the other tissues analyzed. Within the kidney, Cre transcripts were demonstrated to be restricted to the proximal tubule only. iL1-sglt2-Cre mice were bred with ROSA26-LacZ reporter mice that contained a loxP-flanked stop sequence upstream of the LacZ gene. X-gal staining and immunohistochemistry using specific antibodies (anti-megalin, anti-Tamm-Horsfall, anti-NaCl co-transporter, and anti-aquaporin 2) revealed that sglt2 drives Cre functional expression specifically in proximal tubules. The iL1-sglt2-Cre mouse therefore represents a powerful tool for Cre-LoxP-mediated conditional expression in the renal proximal tubule.
A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction
Authors: Luciani R. Carvalho, Kathryn S. Woods, Berenice B. Mendonca, Nathalie Marcal, Andrea L. Zamparini, Stefano Stifani, Joshua M. Brickman, Ivo J.P. Arnhold, Mehul T. Dattani
Journal: Journal of Clinical Investigation (2003)

The paired-like homeobox gene expressed in embryonic stem cells Hesx1/HESX1 encodes a developmental repressor and is expressed in early development in a region fated to form the forebrain, with subsequent localization to Rathke's pouch, the primordium of the anterior pituitary gland. Mutations within the gene have been associated with septo-optic dysplasia, a constellation of phenotypes including eye, forebrain, and pituitary abnormalities, or milder degrees of hypopituitarism. We identified a novel homozygous nonconservative missense mutation (I26T) in the critical Engrailed homology repressor domain (eh1) of HESX1, the first, to our knowledge, to be described in humans, in a girl with evolving combined pituitary hormone deficiency born to consanguineous parents. Neuroimaging revealed a thin pituitary stalk with anterior pituitary hypoplasia and an ectopic posterior pituitary, but no midline or optic nerve abnormalities. This I26T mutation did not affect the DNA-binding ability of HESX1 but led to an impaired ability to recruit the mammalian Groucho homolog/Transducin-like enhancer of split-1 (Gro/TLE1), a crucial corepressor for HESX1, thereby leading to partial loss of repression. Thus, the novel pituitary phenotype highlighted here appears to be a specific consequence of the inability of HESX1 to recruit Groucho-related corepressors, suggesting that other molecular mechanisms govern HESX1 function in the forebrain.
The Niemann-Pick type C2 protein loads isoglobotrihexosylceramide onto CD1d molecules and contributes to the thymic selection of NKT cells
Authors: Nicolas Schrantz, Yuval Sagiv, Yang Liu, Paul B. Savage, Albert Bendelac, Luc Teyton
Journal: The Journal of Experimental Medicine (2007)

The Niemann-Pick type C2 (NPC2) protein is a small, soluble, lysosomal protein important for cholesterol and sphingolipid transport in the lysosome. The immunological phenotype of NPC2-deficient mice was limited to an impaired thymic selection of Vα14 natural killer T cells (NKT cells) and a subsequent reduction of NKT cells in the periphery. The remaining NKT cells failed to produce measurable quantities of interferon-γ in vivo and in vitro after activation with α-galactosylceramide. In addition, thymocytes and splenocytes from NPC2-deficient mice were poor presenters of endogenous and exogenous lipids to CD1d-restricted Vα14 hybridoma cells. Importantly, we determined that similar to saposins, recombinant NPC2 was able to unload lipids from and load lipids into CD1d. This transfer activity was associated with a dimeric form of NPC2, suggesting a unique mechanism of glycosphingolipid transfer by NPC2. Similar to saposin B, NPC2 dimers were able to load isoglobotrihexosylceramide (iGb3), the natural selecting ligand of NKT cells in the thymus, into CD1d. These observations strongly suggested that the phenotype observed in NPC2-deficient animals was directly linked to the efficiency of the loading of iGb3 into CD1d molecules expressed by thymocytes. This conclusion was supported by the rescue of endogenous and exogenous iGb3 presentation by recombinant NPC2. Thus, the loading of endogenous and exogenous lipids and glycolipids onto CD1d is dependent on various small, soluble lipid transfer proteins present in the lysosome.
Safety of formoterol Turbuhaler(R) at cumulative dose of 90 g in patients with acute bronchial obstruction
Authors: J. Malolepszy, G. Böszörményi Nagy, O. Selroos, P. Larsson, R. Brander
Journal: European Respiratory Journal (2001)

This study compared the safety of formoterol (Oxis® Turbuhaler®; 90 µg delivered dose; 120 µg metered dose) with terbutaline (Bricanyl® Turbuhaler®; 10 mg), in patients with acute bronchoconstriction. Forty-eight patients (31 females) with a mean age of 45 yrs, were randomized into two parallel groups (double-blind design). Mean baseline forced expiratory volume in one second (FEV 1 ) was 0.98 L (33% of predicted normal). Study drugs were administered on six occasions during 3 h (formoterol 4.5 µg or terbutaline 0.5 mg·inhalation −1 , 20 inhalations). Patients received intravenous prednisolone after 1.5 h and oxygen during the first 3 h. Pulse rate, serum potassium, 12-lead electrocardiogram (ECG), Holter ECG, arterial blood gases and FEV 1 were assessed during 12 h after the first dose. Four patients (one formoterol, three terbutaline) discontinued. The 12-h mean values of serum potassium decreased from 4.02 to 3.89 mmol·L −1 for formoterol and from 4.22 to 3.76 mmol·L −1 for terbutaline. Mean 12-h pulse rate was significantly (p&lt;0.01) higher in the terbutaline group (101.7 beats per minute (bpm)) than in the formoterol group (93.5 bpm). No individual patient value was considered clinically important or alarming. FEV 1 improved in both groups but with no statistically significant difference between treatments. Oxis® Turbuhaler® (90 µg) was at least as safe and well tolerated as terbutaline (110 mg) in patients with acute bronchoconstriction.
Interaction between isoniazid and diverse vasodilators: role of decreased cerebral GABA
Authors: M de los Angeles Sánchez-Salvatori
Journal: Cardiovascular Research (1998)

Objective: To determine if the interaction between isoniazid and hydralazine, consisting of increased hypotension accompanied by bradycardia, occurs with other vasodilators. Methods: Blood pressure and heart rate responses to a number of vasodilators were determined in rats under chloralose-urethane, pretreated or not with 250 mg/kg of isoniazid. The influence of this dose of isoniazid on GABA levels in the hypothalamus and pons-medulla was assessed in other groups of rats. Results: Increased hypotension and bradycardia following i.p. isoniazid were observed with dipyridamole, prazosin, pinacidil and hydralazine given i.v. Bradycardia without increased hypotension appeared with papaverine and verapamil, while increased hypotension with unchanged heart rate was observed with minoxidil and captopril. Isoniazid decreased GABA in the hypothalamus and pons-medulla. Conclusions: At the high dose used, isoniazid interacts with various vasodilators, irrespective of their mechanism of action. The interaction could be due to the influence of the drug on GABA levels at cardiovascular regulatory sites.
A statistical taxonomy and another “chance” for natural frequencies
Authors: Adrien Barton, Shabnam Mousavi, Jeffrey R. Stevens
Journal: Behavioral and Brain Sciences (2007)

Abstract The conclusions of Barbey &amp; Sloman (B&amp;S) crucially depend on evidence for different representations of statistical information. Unfortunately, a muddled distinction made among these representations calls into question the authors' conclusions. We clarify some notions of statistical representations which are often confused in the literature. These clarifications, combined with new empirical evidence, do not support a dual-process model of judgment.