tbuckley/cabot-search huggingface dataset:
Fall in immune complex levels during gold treatment of rheumatoid arthritis.
Authors: J Highton, G S Panayi, P Shepherd, A Faith, J Griffin, T Gibson
Journal: Annals of the Rheumatic Diseases (1981)

Prior to starting gold treatment 30 patients with rheumatoid arthritis had an elevated mean level of circulating immune complexes measured by Clq binding activity. Gold treatment led to an improvement in disease reflected by significant falls in erythrocyte sedimentation rate (p less than 0.001), C-reactive protein (p less than 0.01), Ritchie articular index (p less than 0.001), and duration of morning stiffness (p less than 0.05). Concurrently immune complex levels fell, and this change first reached significance after 3 months' treatment (p less than 0.05). Serum Clq binding activity was not related to clinical and laboratory measurements of joint inflammation. This suggested to us that there is no direct immunopathological relationship between circulating immune complexes and joint inflammation in rheumatoid arthritis. Serum Clq binding activity was strongly related to IgM-RF levels measured at latex titre (r - 0.7, p less than 0.001). Removal of immune complexes from serum with Sepharose 4B-staph A (staphylococcal protein A) led to a fall in IgM-RF from 2 mg/ml (2 g/l) to 0.4 mg/ml (0.4 g/l). This suggests that the reason for the relationship between Clq BA and IgM-RF is that, on average 80% of serum IgM-RF exists as part of immune complexes containing IgG.
Adenoviral Expression of <i>I</i> <sub>Ks</sub> Contributes to Wavebreak and Fibrillatory Conduction in Neonatal Rat Ventricular Cardiomyocyte Monolayers
Authors: Viviana Muñoz, Krzysztof R. Grzeda, Thomas Desplantez, Sandeep V. Pandit, Sergey Mironov, Steven M. Taffet, Stephan Rohr, André G. Kléber, José Jalife
Journal: Circulation Research (2007)

Previous studies have shown that the gating kinetics of the slow component of the delayed rectifier K + current ( I Ks ) contribute to postrepolarization refractoriness in isolated cardiomyocytes. However, the impact of such kinetics on arrhythmogenesis remains unknown. We surmised that expression of I Ks in rat cardiomyocyte monolayers contributes to wavebreak formation and facilitates fibrillatory conduction by promoting postrepolarization refractoriness. Optical mapping was performed in 44 rat ventricular myocyte monolayers infected with an adenovirus carrying the genomic sequences of KvLQT1 and minK (molecular correlates of I Ks ) and 41 littermate controls infected with a GFP adenovirus. Repetitive bipolar stimulation was applied at increasing frequencies, starting at 1 Hz until loss of 1:1 capture or initiation of reentry. Action potential duration (APD) was significantly shorter in I Ks -infected monolayers than in controls at 1 to 3 Hz ( P &lt;0.05), whereas differences at higher pacing frequencies did not reach statistical significance. Stable rotors occurred in both groups, with significantly higher rotation frequencies, lower conduction velocities, and shorter action potentials in the I Ks group. Wavelengths in the latter were significantly shorter than in controls at all rotation frequencies. Wavebreaks leading to fibrillatory conduction occurred in 45% of the I Ks reentry episodes but in none of the controls. Moreover, the density of wavebreaks increased with time as long as a stable source sustained the fibrillatory activity. These results provide the first demonstration that I Ks -mediated postrepolarization refractoriness can promote wavebreak formation and fibrillatory conduction during pacing and sustained reentry and may have important implications in tachyarrhythmias.
Mechanisms of aging in senescence-accelerated mice
Authors: Todd A Carter, Jennifer A Greenhall, Shigeo Yoshida, Sebastian Fuchs, Robert Helton, Anand Swaroop, David J Lockhart, Carrolee Barlow
Journal: Genome biology (2005)

Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J).The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response.We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases.
Informed learning and conceptual structure: Putting the “birdness” back in the bird
Authors: Kenneth Kurtz
Journal: Behavioral and Brain Sciences (1997)

The computational notion of “trading spaces” is highly relevant to the psychological domain of categorization. The “theory” view of concepts can be interpreted as a recoding view. A design principle for exploiting learned recodings in order to handle the type-2 problem of forming sophisticated concepts is outlined.
Inactivation of Voltage-Gated Cardiac K <sup>+</sup> Channels
Authors: Randall L. Rasmusson, Michael J. Morales, Shimin Wang, Shuguang Liu, Donald L. Campbell, Mulugu V. Brahmajothi, Harold C. Strauss
Journal: Circulation Research (1998)

Abstract —Inactivation is the process by which an open channel enters a stable nonconducting conformation after a depolarizing change in membrane potential. Inactivation is a widespread property of many different types of voltage-gated ion channels. Recent advances in the molecular biology of K + channels have elucidated two mechanistically distinct types of inactivation, N-type and C-type. N-type inactivation involves occlusion of the intracellular mouth of the pore through binding of a short segment of residues at the extreme N-terminal. In contrast to this “tethered ball” mechanism of N-type inactivation, C-type inactivation involves movement of conserved core domain residues that result in closure of the external mouth of the pore. Although C-type inactivation can show rapid kinetics that approach those observed for N-type inactivation, it is often thought of as a slowly developing and slowly recovering process. Current models of C-type inactivation also suggest that this process involves a relatively localized change in conformation of residues near the external mouth of the permeation pathway. The rate of C-type inactivation and recovery can be strongly influenced by other factors, such as N-type inactivation, drug binding, and changes in [K + ] o . These interactions make C-type inactivation an important biophysical process in determining such physiologically important properties as refractoriness and drug binding. C-type inactivation is currently viewed as arising from small-scale rearrangements at the external mouth of the pore. This review will examine the multiplicity of interactions of C-type inactivation with N-terminal–mediated inactivation and drug binding that suggest that our current view of C-type inactivation is incomplete. This review will suggest that C-type inactivation must involve larger-scale movements of transmembrane-spanning domains and that such movements contribute to the diversity of kinetic properties observed for C-type inactivation.
Multimodality endoscopic eradication for neoplastic Barrett oesophagus: results of an European multicentre study (EURO-II)
Authors: K Nadine Phoa, Roos E Pouw, Raf Bisschops, Oliver Pech, Krish Ragunath, Bas L A M Weusten, Brigitte Schumacher, Bjorn Rembacken, Alexander Meining, Helmut Messmann, Erik J Schoon, Liebwin Gossner, Jayan Mannath, C A Seldenrijk, Mike Visser, Toni Lerut, Stefan Seewald, Fiebo J ten Kate, Christian Ell, Horst Neuhaus, Jacques J G H M Bergman
Journal: Gut (2015)

Focal endoscopic resection (ER) followed by radiofrequency ablation (RFA) safely and effectively eradicates Barrett's oesophagus (BO) containing high-grade dysplasia (HGD) and/or early cancer (EC) in smaller studies with limited follow-up. Herein, we report long-term outcomes of combined ER and RFA for BO (HGD and/or EC) from a single-arm multicentre interventional study.In 13 European centres, patients with BO ≤ 12 cm with HGD and/or EC on 2 separate endoscopies were eligible for inclusion. Visible lesions (<2 cm length; <50% circumference) were removed with ER, followed by serial RFA every 3 months (max 5 sessions). Follow-up endoscopy was scheduled at 6 months after the first negative post-treatment endoscopic control and annually thereafter.complete eradication of neoplasia (CE-neo) and intestinal metaplasia (CE-IM); durability of CE-neo and CE-IM (once achieved) during follow-up. Biopsy and resection specimens underwent centralised pathology review.132 patients with median BO length C3M6 were included. After entry-ER in 119 patients (90%) and a median of 3 RFA (IQR 3-4) treatments, CE-neo was achieved in 121/132 (92%) and CE-IM in 115/132 patients (87%), per intention-to-treat analysis. Per-protocol analysis, CE-neo and CE-IM were achieved in 98% and 93%, respectively. After a median of 27 months following the first negative post-treatment endoscopic control, neoplasia and IM recurred in 4% and 8%, respectively. Mild-to-moderate adverse events occurred in 25 patients (19%); all managed conservatively or endoscopically.In patients with early Barrett's neoplasia, intensive multimodality endotherapy consisting of ER combined with RFA is safe and highly effective, and the treatment effect appears to be durable during mid-term follow-up.NTR 1211, http://www.trialregister.nl.
Satellite-based Estimates of Ambient Air Pollution and Global Variations in Childhood Asthma Prevalence
Authors: H. Ross Anderson, Barbara K. Butland, Aaron van Donkelaar, Michael Brauer, David P. Strachan, Tadd Clayton, Rita van Dingenen, Marcus Amann, Bert Brunekreef, Aaron Cohen, Frank Dentener, Christopher Lai, Lok N. Lamsal, Randall V. Martin, ISAAC Phase One
Journal: Environmental Health Perspectives (2012)

The effect of ambient air pollution on global variations and trends in asthma prevalence is unclear.Our goal was to investigate community-level associations between asthma prevalence data from the International Study of Asthma and Allergies in Childhood (ISAAC) and satellite-based estimates of particulate matter with aerodynamic diameter < 2.5 µm (PM₂.₅) and nitrogen dioxide (NO₂), and modelled estimates of ozone.We assigned satellite-based estimates of PM₂.₅ and NO₂ at a spatial resolution of 0.1° × 0.1° and modeled estimates of ozone at a resolution of 1° × 1° to 183 ISAAC centers. We used center-level prevalence of severe asthma as the outcome and multilevel models to adjust for gross national income (GNI) and center- and country-level sex, climate, and population density. We examined associations (adjusting for GNI) between air pollution and asthma prevalence over time in centers with data from ISAAC Phase One (mid-1900s) and Phase Three (2001-2003).For the 13- to 14-year age group (128 centers in 28 countries), the estimated average within-country change in center-level asthma prevalence per 100 children per 10% increase in center-level PM₂.₅ and NO₂ was -0.043 [95% confidence interval (CI): -0.139, 0.053] and 0.017 (95% CI: -0.030, 0.064) respectively. For ozone the estimated change in prevalence per parts per billion by volume was -0.116 (95% CI: -0.234, 0.001). Equivalent results for the 6- to 7-year age group (83 centers in 20 countries), though slightly different, were not significantly positive. For the 13- to 14-year age group, change in center-level asthma prevalence over time per 100 children per 10% increase in PM₂.₅ from Phase One to Phase Three was -0.139 (95% CI: -0.347, 0.068). The corresponding association with ozone (per ppbV) was -0.171 (95% CI: -0.275, -0.067).In contrast to reports from within-community studies of individuals exposed to traffic pollution, we did not find evidence of a positive association between ambient air pollution and asthma prevalence as measured at the community level.
Dissociation of Dopamine from Its Receptor as a Signal in the Pleiotropic Hypothalamic Regulation of Prolactin Secretion*
Authors: GONZALO MARTÍNEZ de la ESCALERA, RICHARD I. WEINER
Journal: Endocrine Reviews (1992)

PROLACTIN secretion is regulated in mammals by both stimulatory and inhibitory hypothalamic hormones. The initial models developed for PRL regulation were based on the assumption that hypothalamic hormones bound to receptors that activated a single signaling pathway and the actions of multiple regulatory hormones would be integrated in an additive manner. However, regulation of PRL secretion from lactotrophs is not simply the algebraic sum of stimulatory and inhibitory actions but rather a highly interactive pleiotropic system. The association of hormones with their receptors is an essential component of their action mediating the regulation of PRL secretion. In addition, dissociation of the inhibitory hormone dopamine from its receptor is also an important physiological signal in PRL secretion. Dopamine tonically suppresses PRL secretion by occupying specific receptors on lactotrophs. The concentration of dopamine in portal blood is sufficient to occupy approximately 80% of D2 dopamine receptors in the anterior pituitary (1), and the degree of inhibition is proportional to receptor occupancy. In addition, lowering the concentration of dopamine results in rapid dissociation of dopamine from its receptor (2). Dissociation from the receptor activates multiple signaling pathways that in turn stimulate PRL secretion during the time in which dopamine concentration is decreased. In addition, shortterm dissociation from the receptor results in the potentiation of the stimulatory action of TRH, an effect that lasts beyond the period of decreased dopamine concentration. It is increasingly clear that signaling pathways interact at every level, from proximal effects on receptor affinity to distal actions on phosphorylation of transcriptional regulatory factors. This review focuses on the current understanding of the integration of activation of multiple signaling pathways on the regulation of PRL secretion.
Thrombin induces collagen gel contraction partially through PAR1 activation and PKC- 
Authors: Q. Fang
Journal: European Respiratory Journal (2004)

The ability of fibroblasts to contract three-dimensional collagen gels has been used as an <i>in vitro</i> model of the tissue contraction which characterises both normal repair and fibrosis. Among its actions, thrombin can activate the protease-activated receptor (PAR)1 and, thereby, stimulate inflammation and repair. The current study evaluated whether thrombin could stimulate fibroblast-mediated collagen gel contraction by activating PAR1 and whether its downstream signalling depends on protein kinase C (PKC)-ϵ. Human foetal lung fibroblasts (HFL-1) were cultured in three-dimensional collagen gels and the area of the gels was measured by image analyser. Both thrombin and TFLLR, a selective PAR1 agonist, stimulated collagen gel contraction mediated by HFL-1. After RNA interference-mediated PAR1 knockdown in HFL-1, both thrombin and the PAR1 agonist-induced gel contraction were partially inhibited (by 22.4±2.2% and 17.6±5.6%, respectively). The gel contraction stimulated by thrombin was also reduced by a nonspecific PKC inhibitor and a calcium-independent PKC-ϵ inhibitor. Both thrombin and TFLLR significantly increased PKC-ϵ activity, and this effect was blocked by PAR1 knockdown. Thrombin stimulates collagen gel contraction at least partially through activation of protease-activated receptor 1 and protein kinase C-ϵ, and may contribute to tissue remodelling in inflammatory airway and lung diseases.
A shake of the head to a wink of the anus
Authors: O M Jones
Journal: Gut (2002)

We read the case report of Malouf and Kamm ( Gut 2001; 48 :728–9) with interest. However, we disagree with some of the science and suggest an alternative explanation for their findings.

Firstly, there is much data to suggest that sympathetic innervation of the internal anal sphincter is in fact excitatory. The paper that they cite1 (from their own institution) showed that noradrenaline, the principal postganglionic neurotransmitter of the sympathetic nervous system, caused contraction of this tissue in vitro. Operative in vivo studies of presacral nerve stimulation have indeed been contradictory, showing both an increase2 and decrease3 in internal anal sphincter tone; this probably reflects little more than differences in stimulation parameters. However, sympathetic blockade effected either by infusion of the α adrenoceptor antagonist phentolamine4 or by high spinal anaesthesia5 produces a significant fall in internal anal sphincter tone. This is evidence …
Arterial Stiffness and Cardiovascular Events
Authors: Gary F. Mitchell, Shih-Jen Hwang, Ramachandran S. Vasan, Martin G. Larson, Michael J. Pencina, Naomi M. Hamburg, Joseph A. Vita, Daniel Levy, Emelia J. Benjamin
Journal: Circulation (2010)

Various measures of arterial stiffness and wave reflection have been proposed as cardiovascular risk markers. Prior studies have not assessed relations of a comprehensive panel of stiffness measures to prognosis in the community.We used proportional hazards models to analyze first-onset major cardiovascular disease events (myocardial infarction, unstable angina, heart failure, or stroke) in relation to arterial stiffness (pulse wave velocity [PWV]), wave reflection (augmentation index, carotid-brachial pressure amplification), and central pulse pressure in 2232 participants (mean age, 63 years; 58% women) in the Framingham Heart Study. During median follow-up of 7.8 (range, 0.2 to 8.9) years, 151 of 2232 participants (6.8%) experienced an event. In multivariable models adjusted for age, sex, systolic blood pressure, use of antihypertensive therapy, total and high-density lipoprotein cholesterol concentrations, smoking, and presence of diabetes mellitus, higher aortic PWV was associated with a 48% increase in cardiovascular disease risk (95% confidence interval, 1.16 to 1.91 per SD; P=0.002). After PWV was added to a standard risk factor model, integrated discrimination improvement was 0.7% (95% confidence interval, 0.05% to 1.3%; P<0.05). In contrast, augmentation index, central pulse pressure, and pulse pressure amplification were not related to cardiovascular disease outcomes in multivariable models.Higher aortic stiffness assessed by PWV is associated with increased risk for a first cardiovascular event. Aortic PWV improves risk prediction when added to standard risk factors and may represent a valuable biomarker of cardiovascular disease risk in the community.
Androgen receptor gene polymorphisms lean mass and performance in young men
Authors: Amelia Guadalupe-Grau, F Germán Rodríguez-González, Cecilia Dorado, Hugo Olmedillas, Teresa Fuentes, Jorge Pérez-Gómez, Safira Delgado-Guerra, Germán Vicente-Rodríguez, Ignacio Ara, Borja Guerra, Rafael Arteaga-Ortiz, José A L Calbet, B Nicolás Díaz-Chico
Journal: British Journal of Sports Medicine (2009)

The exon-1 of the androgen receptor ( AR ) gene contains two repeat length polymorphisms which modify either the amount of AR protein inside the cell ( GGN n , polyglycine) or its transcriptional activity ( CAG n , polyglutamine). Shorter CAG and/or GGN repeats provide stronger androgen signalling and vice versa. To test the hypothesis that CAG and GGN repeat AR polymorphisms affect muscle mass and various variables of muscular strength phenotype traits, the length of CAG and GGN repeats was determined by PCR and fragment analysis and confirmed by DNA sequencing of selected samples in 282 men (28.6±7.6 years). Individuals were grouped as CAG short ( CAG S ) if harbouring repeat lengths of ≤21 and CAG long ( CAG L ) if CAG &gt;21 . GGN was considered short ( GGN S ) or long ( GGN L ) if GGN ≤23 or &gt;23, respectively. No significant differences in lean body mass or fitness were observed between the CAG S and CAG L groups, or between GGN S and GGN L groups, but a trend for a correlation was found for the GGN repeat and lean mass of the extremities (r=−0.11, p=0.06). In summary, the lengths of CAG and GGN repeat of the AR gene do not appear to influence lean mass or fitness in young men.
Inhibition of Tumor Cell Migration by LD22-4, an N-Terminal Fragment of 24-kDa FGF2, Is Mediated by Neuropilin 1
Authors: Ling Zhang, Graham C. Parry, Eugene G. Levin
Journal: Cancer Research (2013)

LD22-4, an 86-amino acid fragment of the basic fibroblast growth factor, is an inhibitor of cell migration. LD22-4 inhibits the migration of various tumor cells, endothelial cells, and fibroblasts in vitro and suppresses tumor growth and angiogenesis in vivo. LD22-4 is effective in the presence of multiple growth factors, either alone or in combination, as well as haptotactic factors. LD22-4 inhibits the rate of malignant gliomas prepared from U87MG cells in an orthotopic mouse model by 90% compared with untreated mice. Using U87MG cells, we identified the LD22-4 membrane receptor as neuropilin 1 (NRP1). The identification of NRP1 as the LD22-4 receptor was based upon mass spectrometric analysis of proteins that bind to LD22-4, immunoprecipitation of an NRP1-LD22-4 complex formed during incubation of LD22-4 with U87MG cells, LD22-4-NRP1 coimmunoprecipitation studies, and binding of LD22-4 to HEK293 cells expressing NRP1. In contrast, NRP1 binding of an inactive mutant of LD22-4 was substantially reduced. As is typical of NRP1-binding proteins, LD22-4 itself binds to heparin and requires heparan sulfate for binding to cells. The addition of heparin to migration assays increased the inhibitory activity of LD22-4. In addition to a heparin-binding region, LD22-4 contains a 5-amino acid C-terminus that matches an NRP1 consensus binding sequence. Thus, direct binding experiments, dependence on heparan sulfate, and the presence of a NRP1 consensus binding sequence indicate that NRP1 is the binding site of LD22-4 and mediates inhibition of cell migration.
Treatment of In-Growing Toe-Nail
Authors: J. W. Browne
Journal: BMJ (1884)

JOORNAL 8b7 microbe constantl associated with Asiatic cholera, from the resarches and discoveries of Koch, must now be admitted.To my mind, how- ever, it is not proved that the bacillus which has been found causes the disease, nor has it been shown, as far as I know, that the same bacillus is not associate(d with so-called sporadic cholera.I look upon the sub- ject of the-gerins of disease as a most intereating and important one, and have no doubt that discoveries in that field will give valuable aid in diagnosis; but that they will gve important help in the pre- vention of disease has yet to be provd.To my mind, it is of far greater importance, in the cause of pre- vention, to find out what conditions of life, in the individual, the home, or the atmosphere, bring about the states of body in which disease-germs flourish, than to discover the germs themselves and follow their natural history.(liven a community like what was seen