tbuckley/cabot-search huggingface dataset:
Recurrent Recruitment of the THAP DNA-Binding Domain and Molecular Domestication of the P-Transposable Element
Authors: H. Quesneville, D. Nouaud, D. Anxolabehere
Journal: Molecular Biology and Evolution (2004)

The recently described THAP domain motif characterizes a DNA-binding domain (DBD) that is widely conserved in human and in animals. It presents a similarity with the DBD of the P element transposase of D. melanogaster. We show here that the P Drosophila neogenes derived from P-transposable elements conserve the THAP domain. Moreover, secondary rearrangements by exon shuffling indicate the recurrent recruitment of this domain by the host genome. As P sequences and THAP genes are found together in many animal genomes, we discuss the possibility that the THAP proteins have acquired their domain as a result of recurrent molecular domestication of P-transposable elements.
Mesolimbic dopamine and the neuropsychology of dreaming: Some caution and reconsiderations
Authors: Fabrizio Doricchi, Cristiano Violani
Journal: Behavioral and Brain Sciences (2000)

New findings point to a role for mesolimbic DA circuits in the generation of dreaming. We disagree with Solms about these structures having an exclusive role in generating dreams. We review data suggesting that dreaming can be interrupted at different levels of processing and that anterior-subcortical lesions associated with dream cessation are unlikely to produce selective hypodopaminergic dynamic impairments. [Hobson et al.; Nielsen; Solms]
Gangrene of the Forearm after Subclavian Arterio-aortostomy for Coarctation of the Aorta
Authors: C. F. Kittle, P. W. Schafer
Journal: Thorax (1953)

Utilization of the subclavian artery in establish- ing an anastomotic shunt between major portions of the cardiovascular system for application to congenital cardiovascular anomalies was first sug- gested by Blalock and Park (1944).Subsequently, its practicability has been demonstrated in un- counted instances, Blalock (1948) and Ravitch (1953) describing over 1,100 cases in which this procedure was used for treating the tetralogy of Fallot.Clagett (1947) first employed subclavian arterio-aortostomy in coarctation of the aorta.Other series discussing the use of subclavian shunts have been reported by Shumacker (1951), Gross (1945), and many others.
Recorded infections and antibiotics in early life: associations with allergy in UK children and their parents
Authors: J. M Harris, P. Mills, C. White, S. Moffat, A. J Newman Taylor, P. Cullinan
Journal: Thorax (2007)

It is suggested that the inverse relationship between allergic disease and family size reflects reduced exposure to early life infections, and that antibiotic treatment in childhood diminishes any protective effect of such infection.A birth cohort study was undertaken in 642 children recruited before birth and seen annually until the age of 8 years. Reported infections and prescribed antibiotics by the age of 5 years were counted from GP records and comparisons were made with a previous study of their parents.At the age of 8 years, 104 children (19%) were atopic, 79 (13%) were currently wheezy and 124 (21%) had seasonal rhinitis. 577 children (97%) had at least three infections recorded by age 5, a figure much higher than that of their parents (69%). By the age of 5 only 11 children (2%) had never received a prescription for antibiotics; the corresponding figure for the parents was 24%. Higher numbers of infections were recorded for firstborn children. After adjusting for parental atopy and birth order, there was no association between infection counts and atopy (OR 1.01 (95% CI 0.99 to 1.03) per infection). Significant positive associations were found for wheeze and seasonal rhinitis. An increased risk of current wheeze was found for each antibiotic prescription (adjusted OR 1.07 (95% CI 1.03 to 1.10)) but not for atopy. This was primarily explained by prescriptions for respiratory infections. Similar patterns were observed for seasonal rhinitis.Despite very high rates of recorded early life infections and antibiotic prescriptions, no plausibly causative relationships were found with subsequent respiratory allergies.
Serine Protease Inhibitor Serp-1 Strongly Impairs Atherosclerotic Lesion Formation and Induces a Stable Plaque Phenotype in ApoE <sup>−/−</sup> Mice
Authors: Ilze Bot, Jan H. von der Thüsen, Marjo M.P.C. Donners, Alexandra Lucas, Madelon L. Fekkes, Saskia C.A. de Jager, Johan Kuiper, Mat J.A.P. Daemen, Theo J.C. van Berkel, Sylvia Heeneman, Erik A.L. Biessen
Journal: Circulation Research (2003)

The myxoma virus protein Serp-1 is a member of the serine protease inhibitor superfamily. Serp-1 potently inhibits human serum proteases including plasmin, urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA). Serp-1 also displays a high antiinflammatory activity, rendering it a promising candidate for antiatherosclerotic therapy. In this study, we have thus examined the effect of Serp-1 on de novo atherosclerotic plaque formation and on advanced lesions. Perivascular collars were placed around carotid arteries of ApoE-/- mice to induce atherosclerotic plaques and Serp-1 treatment started at week 1 and week 5 after collar placement. Effects of Serp-1 on de novo atherogenesis were characterized by a significantly lower plaque size than that of control mice (18+/-5x10(3) versus 57+/-12x10(3) microm2, respectively; P=0.007). Immunostaining showed a 50% (P=0.004) decrease in the MOMA-2-stained lesion area of Serp-1-treated mice. Treatment of advanced lesions with Serp-1 resulted in a decrease in plaque size and lumen stenosis (P=0.028). Alpha-actin staining of these lesions was significantly increased compared with the control (P=0.017). In both studies, a higher cellularity of the plaque and increased collagen content was observed in Serp-1-treated mice. In vitro studies showed that Serp-1 induces proliferation and migration of vascular smooth muscle cells. In conclusion, Serp-1 inhibits carotid artery plaque growth and progression in ApoE-/- mice. Equally relevant, it enhances cellularity of the plaque core potentially leading to improved plaque stability. The above results indicate that Serp-1 constitutes a promising lead in antiatherosclerotic therapy.
Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors
Authors: Johanna C. Bendell, Jordi Rodon, Howard A. Burris, Maja de Jonge, Jaap Verweij, Diana Birle, David Demanse, Stefan S. De Buck, Qinhua C. Ru, Malte Peters, Michael Goldbrunner, José Baselga
Journal: Journal of Clinical Oncology (2011)

This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), safety, preliminary activity, pharmacokinetics (PK), and pharmacodynamics of BKM120, a potent and highly specific oral pan-Class I PI3K inhibitor.Thirty-five patients with advanced solid tumors received daily BKM120 12.5 to 150 mg. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Assessments included archival tumor molecular status, response by Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography tracer uptake ([(18)F]fluorodeoxyglucose positron emission tomography [FDG-PET]), fasting plasma C-peptide, and phosphorylated ribosomal protein S6 (pS6) in skin biopsies.Overall, treatment was well tolerated. Dose-limiting toxicities were grade 2 mood alteration (80 mg), grade 3 epigastralgia, grade 3 rash, grade 2 and grade 3 mood alteration (100 mg), and two grade 4 hyperglycemia (150 mg). The MTD was 100 mg/d. Frequent treatment-related adverse events included rash, hyperglycemia, diarrhea, anorexia, and mood alteration (37% each); nausea (31%); fatigue (26%); pruritus (23%); and mucositis (23%). BKM120 demonstrated rapid absorption, half-life of ∼40 hours, ∼three-fold steady-state accumulation, dose-proportional exposure, and moderate interpatient variability. One patient demonstrated a confirmed partial response (triple-negative breast cancer); seven patients (20%) were on study for ≥ 8 months. BKM120 demonstrated dose-dependent pharmacodynamic effects on [(18)F]FDG-PET, fasting C-peptide, fasting blood glucose, and pS6. No significant trends were seen to correlate tumor molecular alterations with clinical activity.This study demonstrates feasibility and proof-of-concept of class I PI3K inhibition in patients with advanced cancers. BKM120, at the MTD of 100 mg/d, is safe and well tolerated, with a favorable PK profile, clear evidence of target inhibition, and preliminary antitumor activity.
Does active rheumatoid arthritis affect intestinal iron absorption?
Authors: H P Benn, J Drews, G Randzio, J M Jensen, H Loffler
Journal: Annals of the Rheumatic Diseases (1988)

One of the causes of anaemia in rheumatoid arthritis is thought to be defective iron absorption. In this study the 59Fe absorption in patients with active rheumatoid arthritis is measured and correlated with the results for bone marrow iron stores (and in some cases with the iron stores in the terminal duodenum), which were assessed simultaneously with semiquantitative methods, and with the serum ferritin concentration. In 11 patients with rheumatoid arthritis and increased bone marrow iron stores, iron absorption was decreased. In five patients it was normal and in three further patients, whose bone marrow iron stores were depleted, iron absorption was maximally increased. According to the results both intestinal malabsorption and defective iron absorption can be excluded as causes.
Dietary Patterns and the Metabolic Syndrome in Korean Adolescents
Authors: Jeong A Kim, Seon Mee Kim, Jee Sung Lee, Han Jin Oh, Jee Hye Han, Yoonju Song, Hyojee Joung, Hye Soon Park
Journal: Diabetes Care (2007)

The presence of metabolic syndrome in children and adolescents represents a high-risk state that conveys an increased risk of metabolic disease (1,2). The importance of the role of dietary patterns cannot be overemphasized because of the relation to metabolic disease. Although previous studies show that some dietary patterns are related to the risk of the metabolic syndrome (3–6), these studies focus on adults and were rarely conducted on children or adolescents in a nationally based survey. Therefore, the aim of this study was to identify dietary patterns and to examine the association between dietary patterns and the metabolic syndrome in Korean adolescents. Although studies on the Korean population may yield unique results primarily due to the ethnic homogeneity inherent to the Korean population with very little genetic diversity, the results tend to be applicable to other countries as well.

The 2001 Korean National Health and Nutrition Survey, a cross-sectional and nationally representative survey, was conducted from November to December 2001. A stratified, multistage, probability sampling design was used, with selection made from sampling units. Weights indicating the probability of being sampled were assigned to each participant, which enabled the results to represent the entire Korean population.

A total of 12,441 individuals participated in the Health Interview Survey, which included a 24-h dietary intake recall. …
Biomaterials for Mediation of Chemical and Biological Warfare Agents
Authors: Alan J. Russell, Jason A. Berberich, Géraldine F. Drevon, Richard R. Koepsel
Journal: Annual Review of Biomedical Engineering (2003)

▪ Abstract Recent events have emphasized the threat from chemical and biological warfare agents. Within the efforts to counter this threat, the biocatalytic destruction and sensing of chemical and biological weapons has become an important area of focus. The specificity and high catalytic rates of biological catalysts make them appropriate for decommissioning nerve agent stockpiles, counteracting nerve agent attacks, and remediation of organophosphate spills. A number of materials have been prepared containing enzymes for the destruction of and protection against organophosphate nerve agents and biological warfare agents. This review discusses the major chemical and biological warfare agents, decontamination methods, and biomaterials that have potential for the preparation of decontamination wipes, gas filters, column packings, protective wear, and self-decontaminating paints and coatings.
Simulation of Clinical Trials
Authors: N. H. G. Holford, H. C. Kimko, J. P. R. Monteleone, C. C. Peck
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Computer simulation of clinical trials has evolved over the past two decades from a simple instructive game to "full" simulation models yielding pharmacologically sound, realistic trial outcomes. The need to make drug development more efficient and informative and the awareness that many industries make extensive use of simulation in product development have advanced considerably the use of simulation of clinical trials in pharmaceutical product development over the past decade. The structural and stochastic components of trial simulation models are explained as a prelude to a listing of representative simulation projects, reflecting investigative applications of statistical methods, trial design comparisons, and full simulation of new drugs being developed. Lessons learned from these projects are reviewed in the context of their current impact and potential for influencing the future of drug development.
Human IgE+ B cells are derived from T cell–dependent and T cell–independent pathways
Authors: Magdalena A. Berkowska, Jorn J. Heeringa, Enes Hajdarbegovic, Mirjam van der Burg, H. Bing Thio, P. Martin van Hagen, Louis Boon, Alberto Orfao, Jacques J.M. van Dongen, Menno C. van Zelm
Journal: Journal of Allergy and Clinical Immunology (2014)
SOME ASPECTS OF INFANT FEEDING
Authors: H. B. Graham
Journal: BMJ (1935)

MEDICAL JOURNAL, had categorically and correctly announced the cause of scurvy and 162 years after Lind had described its cure, and it was made in the colrse of a researchprimarily undertaken for another purpose.It is difficult not to believe that an active clinical science, by its situation so favourably placed for a direct attack, could have saved some of these long and costly years. REFERENCESThe De fabrica corporis hituwiani of Andreas Vesalius and the De revolution2ibis obi(snii celest'iam of Nicolaus Copernicus.
Forskolin Stimulates Swelling-Induced Chloride Current, Not Cardiac Cystic Fibrosis Transmembrane-Conductance Regulator Current, in Human Cardiac Myocytes
Authors: Mehmet C. Oz, Steve Sorota
Journal: Circulation Research (1995)

Abstract Whole-cell patch clamp was used to look for cystic fibrosis transmembrane-conductance regulator (CFTR)–like chloride currents in calcium-tolerant human cardiac myocytes. Potassium-containing solutions were used initially. Steady state currents were measured with hyperpolarizing ramps (−16.25 mV/s). Peak net inward currents during voltage steps from −50 to +5 mV were used as an index of L-type calcium current. Isoproterenol (1 μmol/L) or forskolin (10 μmol/L) were used in attempts to evoke CFTR-like chloride current. No forskolin- or isoproterenol-induced steady state current was found in any of 17 atrial cells from seven patients in the absence of cell swelling. Every cell exhibited a large increase in net inward current in response to forskolin, suggesting that cAMP-dependent stimulation of L-type calcium current was present. Swelling with osmotic stress induced an outwardly rectifying steady state current with a reversal potential close to the chloride equilibrium potential. Once this current was activated, exposure to forskolin caused a further increase that subsided on washout (four of four cells, two patients). The atrial swelling-induced current was studied in more detail by using cesium-containing solutions. The current was determined to be a chloride current because the reversal potential was sensitive to changes in intracellular chloride and outward currents were blocked by 150 μmol/L DIDS. Ventricular cells were isolated from five failing human hearts. No CFTR-like current was found in any of 17 cells. In eight of eight ventricular cells, a swelling-induced current was found. The amplitude of the swelling-induced current was enhanced by forskolin. In human ventricular cells, outward swelling-induced currents were inhibited by DIDS. The present results are in apparent conflict with mRNA measurements made by others. Our results suggest that significant amounts of functional channels do not accumulate despite the reported presence of cardiac CFTR mRNA in human heart. However, human myocardium does express a swelling-induced chloride current that can be stimulated by forskolin.
Smoking delays gastric emptying of solids.
Authors: G Miller, K R Palmer, B Smith, C Ferrington, M V Merrick
Journal: Gut (1989)

Oesophageal transit and gastric emptying of liquids and solids was measured in eight normal subjects with a single test meal containing In113 labelled water and an omelette labelled with Tc99m sulphur colloid. Each volunteer was studied, basally, whilst continuously smoking, and while chewing nicotine gum. Neither liquid, nor solid oesophageal transit were affected by smoking, or gum. Liquid gastric emptying occurred exponentially and clearance was not affected by smoking nor gum (mean basal t1/2 17.4 (2.7) (SEM) min, smoking t1/2 16.6 (7.4) min, gum t1/2 12.5 (2.9) min). Gastric emptying of solid had three components. An initial mean lag phase increased from 17.5 (2.7) min, to 27.5 (6.1) min (p less than 0.05) during smoking, but was not prolonged by nicotine gum (17.5 (1.1) min). A subsequent linear emptying phase was also slowed by smoking from a mean of 1.01 (0.15)% min to 0.80 (0.15)% min (p less than 0.05), but was not affected by nicotine gum, 1.06 (0.2)% min. A third complex phase of solid gastric emptying was not analysed. Smoking delays gastric emptying of solids, but not liquids; nicotine is not responsible for this effect. This observation may partly explain the adverse effect of smoking in patients with gastro-oesophageal reflux.
Drug-Eluting Stent Update 2007
Authors: Joost Daemen, Patrick W. Serruys
Journal: Circulation (2007)

A nalyst projections for the drug-eluting stent (DES) market estimated that the total number of DES implanted in 2010 would go beyond 4.5 million worldwide.Although the initial results seemed promising, longer-term follow-up in a broader range of patients revealed some pitfalls.][3][4][5][6][7][8] The number of stents currently under investigation is substantial.They are all loaded with drugs that interfere with pathways in the process of inflammation and neointimal proliferation.However, the process of restenosis is a sequence of complex events that has been only partly elucidated over the last 2 decades. 9Locally acting DES provide the opportunity to interfere with the various mechanisms responsible for each step in the restenotic cascade, and a wide variety of different agents are currently available.Although only sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have received US Food and Drug Administration (FDA) approval to date, multiple alternative devices are attempting to find their way to achieve the same goal, namely a reduction of restenosis and the need for repeat interventions. EverolimusA second derivative of the Limus family is everolimus, a sirolimus analog with a single minimal alteration in its
PROGNOSIS IN CONGESTIVE HEART FAILURE
Authors: Thomas S. Rector, Ph.D, Jay N. Cohn, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Prognostic variables such as the ejection fraction and peak oxygen consumption can be used to place patients with heart failure in risk strata. Some vasodilators have been shown to improve survival at all stages of heart failure with the probability of benefit increasing as the prognosis worsens. Quantitative estimates of survival among groups defined by prognostic variables and treatments should be used to make more informed benefit-to-risk assessments.
High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease
Authors: R. Kotlowski, C. N Bernstein, S. Sepehri, D. O Krause
Journal: Gut (2006)

It is not clear which species of bacteria may be involved in inflammatory bowel disease (IBD). One way of determining which bacteria might be likely candidates is to use culture-independent methods to identify microorganisms that are present in diseased tissues but not in controls.(1) To assess the diversity of microbial communities of biopsy tissue using culture-independent methods; (2) to culture the bacteria found in the tissues of patients with IBD but not in the controls; (3) to identify potential virulence factors associated with cultured bacteria.84 biopsy specimens were collected from 15 controls, 13 patients with Crohn's disease (CD) and 19 patients with ulcerative colitis (UC) from a population-based case-control study. Ribosomal intergenic spacer analysis (RISA) was conducted to identify unique DNA bands in tissues from patients with CD and UC that did not appear in controls.RISA followed by DNA sequencing identified unique bands in biopsy specimens from patients with IBD that were classified as Escherichia coli. Targeted culture showed a significantly (p<0.05) higher number of Enterobacteriaceae in specimens from patients with IBD. The B2+D phylogenetic group, serine protease autotransporters (SPATE) and adherence factors were more likely to be associated with tissues from patients with UC and CD than with controls.The abundance of Enterobacteriaceae is 3-4 logs higher in tissues of patients with IBD and the B2+D phylogenetic groups are more prevalent in patients with UC and CD. The B2+D phylogenetic groups are associated with SPATE and adherence factors and may have a significant role in disease aetiology.
G Protein–Coupled Receptor Heteromers
Authors: Ivone Gomes, Mohammed Akli Ayoub, Wakako Fujita, Werner C. Jaeger, Kevin D.G. Pfleger, Lakshmi A. Devi
Journal: The Annual Review of Pharmacology and Toxicology (2015)

G protein-coupled receptors (GPCRs) compose one of the largest families of membrane proteins involved in intracellular signaling. They are involved in numerous physiological and pathological processes and are prime candidates for drug development. Over the past decade, an increasing number of studies have reported heteromerization between GPCRs. Many investigations in heterologous systems have provided important indications of potential novel pharmacology; however, the physiological relevance of these findings has yet to be established with endogenous receptors in native tissues. In this review, we focus on family A GPCRs and describe the techniques and criteria to assess their heteromerization. We conclude that advances in approaches to study receptor complex functionality in heterologous systems, coupled with techniques that enable specific examination of native receptor heteromers in vivo, are likely to establish GPCR heteromers as novel therapeutic targets.
A pilot study of low-dose erythromycin in bronchiectasis
Authors: KW Tsang, PI Ho, KN Chan, MS Ip, WK Lam, CS Ho, KY Yuen, GC Ooi, R Amitani, E Tanaka
Journal: European Respiratory Journal (1999)

Patients with bronchiectasis suffer from sputum production, recurrent exacerbations, and progressive airway destruction. Erythromycin is effective in diffuse panbronchiolitis, another suppurative airway disorder, although its efficacy is unknown in idiopathic bronchiectasis. A double-blind placebo-controlled study was therefore conducted to evaluate the effects of 8-week administration of low dose erythromycin (500 mg b.i.d.) in steady-state idiopathic bronchiectasis. Patients in the erythromycin group (n=11, 8 female, mean age 50+/-15 yrs), but not the placebo group (n=10, 8 female, mean age 59+/-16 yrs) had significantly improved forced expiratory volume in one second, forced vital capacity and 24-h sputum volume after 8 weeks (p&lt;0.05). There was no parallel improvement in sputum pathogens, leukocytes, interleukin (IL)-1alpha and IL-8, tumour necrosis factor-alpha, or leukotriene B4. The results of this pilot study show that low-dose erythromycin improves lung function and sputum volume in bronchiectasis. Further studies are indicated to evaluate the efficacy of long-term erythromycin therapy in bronchiectasis.