tbuckley/cabot-search huggingface dataset:
Copy number of <i>FCGR3B,</i> which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake
Authors: Lisa C. Willcocks, Paul A. Lyons, Menna R. Clatworthy, James I. Robinson, Wanling Yang, Stephen A. Newland, Vincent Plagnol, Naomi N. McGovern, Alison M. Condliffe, Edwin R. Chilvers, Dwomoa Adu, Elaine C. Jolly, Richard Watts, Yu Lung Lau, Ann W. Morgan, Gerard Nash, Kenneth G.C. Smith
Journal: The Journal of Experimental Medicine (2008)

Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcγRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcγRIIIb-deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcγRIIIb. Reduced FcγRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody–associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.
IDENTIFICATION OF A NOVEL CELL TYPE IN PERIPHERAL LYMPHOID ORGANS OF MICE
Authors: Ralph M. Steinman, Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1973)

A novel cell type has been identified in adherent cell populations prepared from mouse peripheral lymphoid organs (spleen, lymph node, Peyer's patch). Though present in small numbers (0.1-1.6% of the total nucleated cells) the cells have distinct morphological features. The nucleus is large, retractile, contorted in shape, and contains small nucleoli (usually two). The abundant cytoplasm is arranged in processes of varying length and width and contains many large spherical mitochondria. In the living state, the cells undergo characteristic movements, and unlike macrophages, do not appear to engage in active endocytosis. The term, dendritic cell, is proposed for this novel cell type.
Velocity of Shortening of Unloaded Heart Muscle and the Length-Tension Relation
Authors: Dirk L. Brutsaert, Victor A. Claes, Edmund H. Sonnenblick
Journal: Circulation Research (1971)

A new technique permits removal of the resting force from the muscle during the course of shortening and study of the maximum velocity of shortening with almost zero load at physiological initial muscle lengths. This unloading has been performed as a sudden unloading to zero total load (zero load clamping), or according to the resting length-tension relations, or according to an arbitrary unloading intermediate between both former modes of unloading. Using these various modes of unloading to zero load during shortening, it has been demonstrated that the maximum velocity of shortening V max remains constant between maximum length (l max ) and a length 12.5% shorter than l max . This unique force (zero load)-velocity (V max )-length (up to 12.5% below l max ) relation is independent of die initial muscle length over this range of lengths, independent of the time after the stimulus over the largest portion of the shortening phase, and independent of the sequence of length change and mode of unloading through which it arrived at zero load within this range of lengths.
Self-Reported Past Gestational Diabetes Mellitus as a Risk Factor for Abnormal Glucose Tolerance Among Australian Women
Authors: David Simmons, Simon Eaton, Jonathan Shaw, Paul Zimmet
Journal: Diabetes Care (2007)

At least 50% of women who have a pregnancy complicated by gestational diabetes mellitus (GDM) progress to permanent type 2 diabetes (1). While few long-term studies have been undertaken (2), progression from GDM to abnormal glucose tolerance (AGT) may not occur in all women. We hypothesized that if AGT occurs, then progression to diabetes would be more likely and that a greater excess of diabetes rather than impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) would occur over time. We used two cohorts of Australian women who participated in either AusDiab (Australian Diabetes, Obesity and Lifestyle Study) (3,4) or CUDS (Crossroads Undiagnosed Disease Study) (5) to investigate the relationship between current glucose tolerance status and self-reported history of diagnosis of GDM.

AusDiab (May 1999 though December 2000) involved 42 randomly selected areas across Australia, and CUDS (June 2001 through March 2003) randomly selected households across six small towns and a regional center in rural Victoria, Australia (3–5). Both studies included residents aged ≥25 years within a household who responded to an initial census and used identical questionnaires and laboratories (and much of the same staff) for sample analysis. Attendance rates for women were 58% ( n = 6,198) and …
Proactive treatment appears to decrease serum immunoglobulin-E levels in patients with severe atopic dermatitis
Authors: T. Fukuie, I. Nomura, K. Horimukai, A. Manki, I. Masuko, M. Futamura, M. Narita, T. Ohzeki, K. Matsumoto, H. Saito, Y. Ohya
Journal: British Journal of Dermatology (2010)

Fig S1. Our standard protocol for proactive treatment of atopic dermatitis. Fig S2. Patient flow. Table S1. Stratified analysis of the two groups. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effect of whole body vibrations on performance indexes of aerobic power and flexibility in non-athlete men
Authors: Babak Davoodi, Sajad Arshadi, Shirin Zilaei Bouri
Journal: British Journal of Sports Medicine (2010)

The aim of the present study was to investigate the effect of one session whole body vibration (WBV) on anaerobic power and flexibility in non-athletic male students. The participants were 12 untrained healthy male students (age: 25.42 years; body mass: 72.99 kg; height: 175.92 cm and body fat percentage: 19.69%). On the day of assessment, the subjects carried out 10 min-warm-up including jogging, stretching and cycling on ergometer. Then, several tests were carried out; vertical jumping test for assessing power, distance jumping test for assessing explosive power and sit and reach test for assessing flexibility. After that, the vibration with frequency 30 Hz and amplitude 10 mm was conducted eight times including 1-min vibration along with 1-min rest lasting for 15 min. After a 5-min cool down, the test of vertical test, distance jump and flexibility was repeated. The results showed that one session of WBV leads to a significant increase in the amount of vertical jump (p=0.009), peak and aerobic power (p=0.002) and flexibility (p=0.005). However, there was no significant increase in distance jump after WBV (p=0.063). Therefore, we concluded that one session of WBV would lead to an increase in anaerobic power, which can be due to neural activation of fast twitch motor units. The increase in flexibility was attributed to the neuromuscular facilitation resulting from WBV.
Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus
Authors: Damian C. Melles, Raymond F.J. Gorkink, Hélène A.M. Boelens, Susan V. Snijders, Justine K. Peeters, Michael J. Moorhouse, Peter J. van der Spek, Willem B. van Leeuwen, Guus Simons, Henri A. Verbrugh, Alex van Belkum
Journal: Journal of Clinical Investigation (2004)

The population structure of Staphylococcus aureus carried by healthy humans was determined using a large strain collection of nonclinical origin (n = 829). High-throughput amplified fragment length polymorphism (AFLP) analysis revealed 3 major and 2 minor genetic clusters of S. aureus, which were corroborated by multilocus sequence typing. Major AFLP cluster I comprised 44.4% of the carriage isolates and showed additional heterogeneity whereas major AFLP groups II and III presented 2 homogeneous clusters, including 47.3% of all carriage isolates. Coanalysis of invasive S. aureus strains and epidemic methicillin-resistant S. aureus (MRSA) revealed that all major clusters contained invasive and multiresistant isolates. However, clusters and subclusters with overrepresentation of invasive isolates were also identified. Bacteremia in elderly adults, for instance, was caused by a IVa cluster–derived strain significantly more often than by strains from other AFLP clusters. Furthermore, expansion of multiresistant clones or clones associated with skin disease (impetigo) was detected, which suggests that epidemic potential is present in pathogenic strains of S. aureus. In addition, the virulence gene encoding Panton-Valentine leukocidin was significantly enriched in S. aureus strains causing abscesses and arthritis in comparison with the carriage group. We provide evidence that essentially any S. aureus genotype carried by humans can transform into a life-threatening human pathogen but that certain clones are more virulent than others.
Mouse Model of Airway Remodeling
Authors: Kazuhiko Shinagawa, Masami Kojima
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased collagen depositions were observed after 12 weeks' antigen exposure. Persistent airway hyperresponsiveness (AHR) was observed in chronically antigen-exposed A/J mice. Eosinophilic inflammation, collagen deposition, and airway wall thickening were all less marked in BALB/c mice than in A/J mice, and no AHR was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway wall thickening, and AHR were not observed at all, although slightly increased collagen deposition was observed. Thus, we found that these changes were strain-dependent. On the other hand, in A/J mice inhalational antigen challenge after ovalbumin/alum immunization led only to a transient increase in eosinophils and to less airway wall thickening, indicating the importance of the protocol used. Use of A/J mice and giving antigen by instillation via the nose is to be recommended for studies of the mechanisms underlying asthma. In particular, useful qualitative and quantitative information relating to the structural and histologic changes in the lungs may be obtainable using this model.
Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2
Authors: G. S. Collins, D. G. Altman
Journal: BMJ (2012)

<b>Objective</b> To evaluate the performance of the QRISK2-2011 score for predicting the 10 year risk of cardiovascular disease in an independent UK cohort of patients from general practice and to compare it with earlier versions of the model and a National Institute for Health and Clinical Excellence version of the Framingham equation. <b>Design</b> Prospective cohort study to validate a cardiovascular risk score with routinely collected data between June 1994 and June 2008. <b>Setting</b> 364 practices from the United Kingdom contributing to The Health Improvement Network (THIN) database. <b>Participants</b> Two million patients aged 30 to 84 years (11.8 million person years) with 93 564 cardiovascular events. <b>Main outcome measure</b> First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records. <b>Results</b> Results from this independent and external validation of QRISK2-2011 indicate good performance data when compared with the NICE version of the Framingham equation. QRISK2-2011 had better ability to identify those at high risk of developing cardiovascular disease than did the NICE Framingham equation. QRISK2-2011 is well calibrated, with reasonable agreement between observed and predicted outcomes, whereas the NICE Framingham equation seems to consistently over-predict risk in men by about 5% and shows poor calibration in women. <b>Conclusions</b> QRISK2-2011 seems to be a useful model, with good discriminative and calibration properties when compared with the NICE version of the Framingham equation. Furthermore, based on current high risk thresholds, concerns exist on the clinical usefulness of the NICE version of the Framingham equation for identifying women at high risk of developing cardiovascular disease. At current thresholds the NICE version of the Framingham equation has no clinical benefit in either men or women.
Restricted Expression of <i>miR-30c-2-3p</i> and <i>miR-30a-3p</i> in Clear Cell Renal Cell Carcinomas Enhances HIF2α Activity
Authors: Lijoy K. Mathew, Samuel S. Lee, Nicolas Skuli, Shilpa Rao, Brian Keith, Katherine L. Nathanson, Priti Lal, M. Celeste Simon
Journal: Cancer Discovery (2013)

Inactivation of the von-Hippel Lindau (VHL) tumor suppressor gene occurs in 90% of human clear cell renal cell carcinomas (ccRCC) and leads to the stable expression of the hypoxia-inducible factors HIF1α and HIF2α. The constitutive expression of HIF1α in a majority of VHL-deficient tumors is counterintuitive, given that HIF1α functions as a tumor suppressor in ccRCC, whereas HIF2α clearly enhances tumor growth. We demonstrate here that miR-30c-2-3p and miR-30a-3p specifically bind and inhibit expression of HIF2A transcripts, and that the locus encoding miR-30c-2-3p and miR-30a-3p is selectively repressed in "H1H2" VHL-deficient tumors expressing both HIF1α and HIF2α proteins. Inhibiting miR-30a-3p expression increases HIF2α levels in H1H2 ccRCC cells and promotes cellular proliferation, angiogenesis, and xenograft tumor growth. Our results indicate that miR-30c-2-3p and miR-30a-3p repression enhances HIF2α expression and suggests a mechanism whereby the tumor-suppressive effects of constitutive HIF1α expression are attenuated in VHL-deficient H1H2 tumors.
Blockade of Calcium Influx through L-Type Calcium Channels Attenuates Mitochondrial Injury and Apoptosis in Hypoxic Renal Tubular Cells
Authors: Tetsuhiro Tanaka, Masaomi Nangaku, Toshio Miyata, Reiko Inagi, Takamoto Ohse, Julie R. Ingelfinger, Toshiro Fujita
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. In hypoxia, ATP depletion causes cellular Ca2+ increase, mitochondrial injury, and apoptosis in renal tubular cells. However, the molecular basis of these observations is incompletely delineated. IRPTC, a rat renal proximal tubular cell line, was treated with antimycin A, and disturbances in cytoplasmic calcium ([Ca2+]c) and mitochondrial calcium ion concentration ([Ca2+]m), dissipation of mitochondrial membrane potential (ΔΨm), cytochrome c release, and resultant apoptosis were examined. Pharmacologic targeting of L-type Ca2+ channels in vitro and in vivo was used to clarify the involvement of voltage-dependent Ca2+ channels during this process. In vitro studies indicated that ATP depletion–induced apoptosis was preceded by increased [Ca2+]c and [Ca2+]m before activation of mitochondrial signaling. Antagonizing L-type Ca2+ channels offset these findings, suggesting [Ca2+]c and [Ca2+]m involvement. Azelnidipine administration ameliorated cellular and mitochondrial Ca2+ accumulation, mitochondrial permeability transition, cytochrome c release, caspase-9 activation, and resultant apoptosis (15.8 ± 0.8% versus 8.9 ± 0.7%; P < 0.01). Similar effects of azelnidipine were substantiated in an in vivo ischemia/reperfusion injury model. There were fewer terminal-deoxynucleotidyl transferase mediated dUTP nick-end labeling–positive cells in the azelnidipine-treated group (0.322 ± 0.038/tubule) as compared with the vehicle-treated group (0.450 ± 0.041; P < 0.05), although the antiapoptotic effect was smaller in vivo than in vitro, partly as a result of distinct levels of Bax expression. It is proposed that voltage-dependent Ca2+ channels are involved in cellular and mitochondrial accumulation of Ca2+ subsequent to ATP depletion and play an important role in regulating mitochondrial permeability transition, cytochrome c release, caspase activation, and apoptosis.
NHS reforms have made complaining more confusing for patients
Authors: A. O'Dowd
Journal: BMJ (2014)

Patients are more confused as to how to complain about problems they experience with the health service after NHS changes introduced last year, MPs have been told. The confusion was partly due to ignorance about NHS commissioning, witnesses told the parliamentary health committee during an evidence session on 8 July for its inquiry into complaints and raising concerns.

MPs asked whether patients got enough help in accessing and using the complaints system and whether they were confused by the “complexity of new commissioning arrangements” in the NHS.

Rob Webster, chief executive of the NHS Confederation, which represents most NHS organisations, giving evidence, said, “I don’t think there’s a widely held understanding of what the role of commissioners …
Aryl hydrocarbon receptor-mediated activity of particulate organic matter from the Paso del Norte airshed along the U.S.-Mexico border.
Authors: Daniel E Arrieta, Cynthia C Ontiveros, Wen-Whai Li, Jose H Garcia, Michael S Denison, Jacob D McDonald, Scott W Burchiel, Barbara Shayne Washburn
Journal: Environmental Health Perspectives (2003)

In this study, we determined the biologic activity of dichloromethane-extracted particulate matter < 10 micro m in aerodynamic diameter (PM10) obtained from filters at three sites in the Paso del Norte airshed, which includes El Paso, Texas, USA; Juarez, Chihuahua, Mexico, and Sunland Park, New Mexico, USA. The extracts were rich in polycyclic aromatic hydrocarbons (PAHs) and had significant biologic activity, measured using two in vitro assay systems: ethoxyresorufin-(O-deethylase (EROD) induction and the aryl hydrocarbon-receptor luciferase reporter system. In most cases, both EROD (5.25 pmol/min/mg protein) and luciferase activities (994 relative light units/mg) were highest in extracts from the Advance site located in an industrial neighborhood in Juarez. These values represented 58% and 55%, respectively, of induction associated with 1 micro M ss-naphthoflavone exposures. In contrast, little activity was observed at the Northeast Clinic site in El Paso, the reference site. In most cases, luciferase and EROD activity from extracts collected from the Tillman Health Center site, situated in downtown El Paso, fell between those observed at the other two sites. Overall, a statistically significant correlation existed between PM10 and EROD and luciferase activities. Chemical analysis of extracts collected from the Advance site demonstrated that concentrations of most PAHs were higher than those reported in most other metropolitan areas in the United States. Calculations made with these data suggest a cancer risk of 5-12 cases per 100,000 people. This risk estimate, as well as comparisons with the work of other investigators, raises concern regarding the potential for adverse health effects to the residents of this airshed. Further work is needed to understand the sources, exposure, and effects of PM10 and particulate organic material in the Paso del Norte airshed.
Intensive versus Conventional Glucose Control in Critically Ill Patients
Authors: Nice-Sugar Study Investigators, D. Chittock, S. Su, D. Blair, D. Foster, Rinaldo Bellomo, D. Cook, V. Dhingra, P. Dodek, P. Hebert, W. Henderson, Stephane Heritier, D. Heyland, C. McArthur, E. McDonald, I. Mitchell, R Norton, J. Potter, B. Robinson, J. Ronco
Journal: New England Journal of Medicine (2009)

Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization.
Long-Term Effects of Pravastatin on Plasma Concentration of C-reactive Protein
Authors: Paul M. Ridker, Nader Rifai, Marc A. Pfeffer, Frank Sacks, Eugene Braunwald
Journal: Circulation (1999)

Background —Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that reduces cardiovascular risk, might alter levels of this inflammatory parameter. Methods and Results —CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated ( r =0.60, P &lt;0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, +4.2%; P =0.2 and mean change, +0.07 mg/dL; P =0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, −17.4%; P =0.004 and mean change, −0.07 mg/dL; P =0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, −21.6%; P =0.007), mean CRP levels (difference, −37.8%; P =0.002), and absolute mean change in CRP (difference, −0.137 mg/dL; P =0.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. Conclusions —Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.