tbuckley/cabot-search huggingface dataset:
Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis
Authors: Nicholas L. Mills, Håkan Törnqvist, Simon D. Robinson, Manuel Gonzalez, Kareen Darnley, William MacNee, Nicholas A. Boon, Ken Donaldson, Anders Blomberg, Thomas Sandstrom, David E. Newby
Journal: Circulation (2005)

Background— Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. Methods and Results— In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 μg/m 3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 μg/min), sodium nitroprusside (2 to 8 μg/min), and verapamil (10 to 100 μg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator ( P &lt;0.0001 for all), this response was attenuated with bradykinin ( P &lt;0.05), acetylcholine ( P &lt;0.05), and sodium nitroprusside ( P &lt;0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator ( P &lt;0.0001) that was suppressed 6 hours after exposure to diesel ( P &lt;0.001; area under the curve decreased by 34%). Conclusions— At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.
Towards accurate imputation of quantitative genetic interactions
Authors: Igor Ulitsky, Nevan J Krogan, Ron Shamir
Journal: Genome biology (2009)

Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae. However, these assays often fail to measure the genetic interactions among up to 40% of the studied gene pairs. Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions.
IMMUNOLOGIC MEMORY CELLS OF BONE MARROW ORIGIN
Authors: Harold C. Miller, Gustavo Cudkowicz
Journal: The Journal of Experimental Medicine (1972)

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F(1) mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process.
On the applicability of the CASPAR criteria in psoriatic arthritis
Authors: O B Pedersen, P Junker
Journal: Annals of the Rheumatic Diseases (2008)

While conducting a cross-sectional, population based twin study on psoriatic arthritis (PsA),1 we concurrently adopted the items required for the classification of PsA according to the Moll and Wright (M&W) definition,2 the Vasey and Espinoza (V&E) criteria3 and the CASPAR criteria.4 The study was based on questionnaire surveys to all Danish twins. This method identified 228 twins with self-reported PsA. After subsequent invitation, 164 twins participated in the diagnostic validation that included telephone interview, scrutiny of medical files, structured interview, clinical examination and serological tests for rheumatoid factor.

#### Box 1 Modified CASPAR criteria (proposed modifications in italics)

To meet the CASPAR (Classification criteria for Psoriatic ARthritis) criteria, a patient must have inflammatory articular disease (joint, spine or enthesal) at current …
Endocrine Factors in Common Epithelial Ovarian Cancer*
Authors: B. RAMANATH RAO, BEREND J. SLOTMAN
Journal: Endocrine Reviews (1991)

THE OVARIES are specialized organs of reproduction, liberating gametes for fertilization and producing hormones, which may act in various genital and nongenital tissues. A number of different cell types are present in the functioning ovary: epithelial cells, stromal cells, and germ cells. Although all cell types may undergo malignant transformation, the vast majority of neoplastic ovarian tumors are of the epithelial type, and it is this type of tumor that will be discussed in this paper. Epithelial ovarian tumors are derived from the surface epithelium of the ovary, which is the adult equivalent of the mesothelium of the embryonic gonad (Müllerian epithelium). There is a close relationship between epithelial tumors and the Müllerian epithelium. Serous tumors resemble the epithelium of the Fallopian tube; endometrioid and clear cell tumors resemble the endometrium; and mucinous tumors resemble the endocervical epithelium. In females, ovarian cancer accounts for 4% of cancers and 6% of cancer deaths (1). The mortality rate from ovarian cancer is higher than for cervical and endometrial cancer combined. Current treatment of ovarian cancer consists of surgery, usually followed by cisplatin-based combination chemotherapy (2).
General practice is just as pressured as emergency departments, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2013)

General practice in England is under as much pressure as hospital emergency departments are, and the narrow focus on solving problems in emergency services could undermine the NHS as a whole, MPs have been told.

During an evidence session of the parliamentary Health Committee’s inquiry into emergency services and care, MPs asked witnesses their views on whether the new processes for commissioning services for emergency and urgent care under the NHS reorganisation were fit for purpose.

Claire Gerada, chairwoman of the Royal College of General Practitioners, said, “We must make sure that we commission an integrated approach to urgent …
Modulation of the Ca <sup>2</sup> Permeable Cation Channel TRPV4 by Cytochrome P450 Epoxygenases in Vascular Endothelium
Authors: J. Vriens, G. Owsianik, B. Fisslthaler, M. Suzuki, A. Janssens, T. Voets, C. Morisseau, B.D. Hammock, I. Fleming, R. Busse, B. Nilius
Journal: Circulation Research (2005)

TRPV4 is a broadly expressed Ca2+-permeable cation channel in the vanilloid subfamily of transient receptor potential channels. TRPV4 gates in response to a large variety of stimuli, including cell swelling, warm temperatures, the synthetic phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), and the endogenous lipid arachidonic acid (AA). Activation by cell swelling and AA requires cytochrome P450 (CYP) epoxygenase activity to convert AA to epoxyeicosatrienoic acids (EETs) such as 5,6-EET, 8,9-EET, which both act as direct TRPV4 agonists. To evaluate the role of TRPV4 and its modulation by the CYP pathway in vascular endothelial cells, we performed Ca2+ imaging and patch-clamp measurements on mouse aortic endothelial cells (MAECs) isolated from wild-type and TRPV4(-/-) mice. All TRPV4-activating stimuli induced robust Ca2+ responses in wild-type MAECs but not in MAECs isolated from TRPV4(-/-) mice. Upregulation of CYP2C expression by preincubation with nifedipine enhanced the responses to AA and cell swelling in wild-type MAECs, whereas responses to other stimuli remained unaffected. Conversely, inhibition of CYP2C9 activity with sulfaphenazole abolished the responses to AA and hypotonic solution (HTS). Moreover, suppression of EET hydrolysis using 1-adamantyl-3-cyclo-hexylurea or indomethacin, inhibitors of soluble epoxide hydrolases (sEHs), and cyclooxygenases, respectively, enhanced the TRPV4-dependent responses to AA, HTS, and EETs but not those to 4alpha-PDD or heat. Together, our data establish that CYP-derived EETs modulate the activity of TRPV4 channels in endothelial cells and shows the unraveling of novel modulatory pathways via CYP2C modulation and sEH inhibition.
Toll-like receptors and microbial exposure: gene-gene and gene-environment interaction in the development of atopy
Authors: N.E. Reijmerink, M. Kerkhof, R.W.B. Bottema, J. Gerritsen, F.F. Stelma, C. Thijs, C.P. van Schayck, H.A. Smit, B. Brunekreef, D.S. Postma, G.H. Koppelman
Journal: European Respiratory Journal (2011)

Environmental and genetic factors contribute to atopy development. High microbial exposure may confer a protective effect on atopy. Toll-like receptors (TLRs) bind microbial products and are important in activating the immune system. To assess whether interactions between microbial exposures and genes encoding TLRs (and related genes) result in atopy, genes, environmental factors and gene–environment interactions of 66 single-nucleotide polymorphisms (SNPs) of 12 genes ( TLR 1 – 6 , 9 and 10 , CD14 , MD2 , lipopolysaccharide-binding protein ( LBP ) and Dectin-1 ), and six proxy parameters of microbial exposure (sibship size, pets (three different parameters), day-care and intrauterine and childhood tobacco smoke exposure) were analysed for association with atopic phenotypes in 3,062 Dutch children (the Allergenic study). The presence of two or more older siblings increased the risk of developing high total immunoglobulin (Ig)E levels at different ages. This risk increased further in children aged 1–2 yrs carrying the minor allele of TLR6 SNP rs1039559. Furthermore, novel two- and three-factor gene–gene and gene–environment interactions were found ( e.g . between sibship size, day-care and LBP SNP rs2232596). Larger sibship size is associated with increased total IgE levels. Furthermore, complex two- and three-factor interactions exist between genes and the environment. The TLRs and related genes interact with proxy parameters of high microbial exposure in atopy development.
High-Risk Ovarian Cancer Based on 126-Gene Expression Signature Is Uniquely Characterized by Downregulation of Antigen Presentation Pathway
Authors: Kosuke Yoshihara, Tatsuhiko Tsunoda, Daichi Shigemizu, Hiroyuki Fujiwara, Masayuki Hatae, Hisaya Fujiwara, Hideaki Masuzaki, Hidetaka Katabuchi, Yosuke Kawakami, Aikou Okamoto, Takayoshi Nogawa, Noriomi Matsumura, Yasuhiro Udagawa, Tsuyoshi Saito, Hiroaki Itamochi, Masashi Takano, Etsuko Miyagi, Tamotsu Sudo, Kimio Ushijima, Haruko Iwase, Hiroyuki Seki, Yasuhisa Terao, Takayuki Enomoto, Mikio Mikami, Kohei Akazawa, Hitoshi Tsuda, Takuya Moriya, Atsushi Tajima, Ituro Inoue, Kenichi Tanaka
Journal: Clinical Cancer Research (2012)

High-grade serous ovarian cancers are heterogeneous not only in terms of clinical outcome but also at the molecular level. Our aim was to establish a novel risk classification system based on a gene expression signature for predicting overall survival, leading to suggesting novel therapeutic strategies for high-risk patients.In this large-scale cross-platform study of six microarray data sets consisting of 1,054 ovarian cancer patients, we developed a gene expression signature for predicting overall survival by applying elastic net and 10-fold cross-validation to a Japanese data set A (n = 260) and evaluated the signature in five other data sets. Subsequently, we investigated differences in the biological characteristics between high- and low-risk ovarian cancer groups.An elastic net analysis identified a 126-gene expression signature for predicting overall survival in patients with ovarian cancer using the Japanese data set A (multivariate analysis, P = 4 × 10(-20)). We validated its predictive ability with five other data sets using multivariate analysis (Tothill's data set, P = 1 × 10(-5); Bonome's data set, P = 0.0033; Dressman's data set, P = 0.0016; TCGA data set, P = 0.0027; Japanese data set B, P = 0.021). Through gene ontology and pathway analyses, we identified a significant reduction in expression of immune-response-related genes, especially on the antigen presentation pathway, in high-risk ovarian cancer patients.This risk classification based on the 126-gene expression signature is an accurate predictor of clinical outcome in patients with advanced stage high-grade serous ovarian cancer and has the potential to develop new therapeutic strategies for high-grade serous ovarian cancer patients.
Randomized, Double-Blind, Placebo-Controlled Trial of Oral Sirolimus for Restenosis Prevention in Patients With In-Stent Restenosis
Authors: Jörg Hausleiter, Adnan Kastrati, Julinda Mehilli, Michael Vogeser, Dietlind Zohlnhöfer, Helmut Schühlen, Christoph Goos, Jürgen Pache, Franz Dotzer, Gisela Pogatsa-Murray, Josef Dirschinger, Uwe Heemann, Albert Schömig
Journal: Circulation (2004)

Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR.Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (P=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (P=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (P<0.001).In patients with ISR, an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis.
Significant and serious dehydration does not affect skeletal muscle cramp threshold frequency
Authors: Kyle W Braulick, Kevin C Miller, Jay M Albrecht, Jared M Tucker, James E Deal
Journal: British Journal of Sports Medicine (2012)

Many clinicians believe that exercise-associated muscle cramps (EAMC) occur because of dehydration. Experimental research supporting this theory is lacking. Mild hypohydration (3% body mass loss) does not alter threshold frequency (TF), a measure of cramp susceptibility, when fatigue and exercise intensity are controlled. No experimental research has examined TF following significant (3-5% body mass loss) or serious hypohydration (>5% body mass loss). Determine if significant or serious hypohydration, with moderate electrolyte losses, decreases TF.A prepost experimental design was used. Dominant limb flexor hallucis brevis cramp TF, cramp electromyography (EMG) amplitude and cramp intensity were measured in 10 euhydrated, unacclimated men (age=24±4 years, height=184.2±4.8 cm, mass=84.8±11.4 kg). Subjects alternated exercising with their non-dominant limb or upper body on a cycle ergometer every 15 min at a moderate intensity until 5% body mass loss or volitional exhaustion (3.8±0.8 h; 39.1±1.5°C; humidity 18.4±3%). Cramp variables were reassessed posthypohydration.Subjects were well hydrated at the study's onset (urine specific gravity=1.005±0.002). They lost 4.7±0.5% of their body mass (3.9±0.5 litres of fluid), 4.0±1.5 g of Na(+) and 0.6±0.1 g K(+) via exercise-induced sweating. Significant (n=5) or serious hypohydration (n=5) did not alter cramp TF (euhydrated=15±5 Hz, hypohydrated=13±6 Hz; F1,9=3.0, p=0.12), cramp intensity (euhydrated= 94.2±41%, hypohydrated=115.9±73%; F1,9=1.9, p=0.2) or cramp EMG amplitude (euhydrated=0.18±0.06 µV, hypohydrated= 0.18±0.09 µV; F1,9=0.1, p=0.79).Significant and serious hypohydration with moderate electrolyte losses does not alter cramp susceptibility when fatigue and exercise intensity are controlled. Neuromuscular control may be more important in the onset of muscle cramps than dehydration or electrolyte losses.
An ultrasonographic study of metatarsophalangeal joint pain: synovitis, structural pathology and their relationship to symptoms and function
Authors: H. I. Keen, A. Redmond, R. J. Wakefield, J. Freeston, A. J. Grainger, E. M. A. Hensor, P. Emery, P. G. Conaghan
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Pain in the first metatarsophalangeal joint (MTPJ) is common, though the link between pathology and symptoms is poorly understood. <h3>Objectives</h3> To examine the relationship between pain, function and ultrasound (US)-detected pathology in the first MTPJ. <h3>Methods</h3> 33 subjects with first MTPJ pain and 20 asymptomatic controls completed questionnaires about pain and function, then underwent clinical examination, US examination and objective assessment of function using a motion tracking system. <h3>Results</h3> Low-level grey scale synovitis and osteophytes were common in patients and controls. Osteophytes were more prevalent in symptomatic first MTPJ [24/33 (73%) vs. 7/20 (35%), p=0.007], and greater osteophyte numbers were weakly associated with higher levels of pain [increase in pain VAS per osteophyte (95% CI)=13.78mm (0.12mm-27.43mm), p=0.048]. A power Doppler (PD) signal was present in a fifth of painful first MTPJs and absent in controls. A PD signal was associated with osteophytes and joint space narrowing but was not independently related to target joint pain. For all first MTPJs, osteophytes and the presence of a PD signal was associated with worse patient-reported function. US features did not predict objective function. <h3>Conclusion</h3> Osteophytes, representing subchondral bone remodelling, were associated with the presence of first MTPJ pain and, together with more severe (PD) synovitis, also contributed to poorer function. Detailed imaging of bone may provide more information on peripheral pain associations.
Erythropoietic protoporphyria exacerbated by oral iron therapy
Authors: A. MILLIGAN, R.A.C. GRAHAM-BROWN, I. SARKANY, H. BAKER
Journal: British Journal of Dermatology (1988)

Journal Article Erythropoietic protoporphyria exacerbated by oral iron therapy Get access A. MILLIGAN, A. MILLIGAN Department of Dermatology, Leicester Royal Infirmary, London Dr Alex Milligan, Department of Dermatology, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.A.C. GRAHAM‐BROWN, R.A.C. GRAHAM‐BROWN Department of Dermatology, Leicester Royal Infirmary, London Search for other works by this author on: Oxford Academic Google Scholar I. SARKANY, I. SARKANY Royal Free Hospital, London Search for other works by this author on: Oxford Academic Google Scholar H. BAKER H. BAKER The London Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue 1, 1 July 1988, Pages 63–66, https://doi.org/10.1111/j.1365-2133.1988.tb07102.x Published: 01 July 1988
Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review
Authors: John Hutchinson, Andrew Fogarty, Richard Hubbard, Tricia McKeever
Journal: European Respiratory Journal (2015)

As idiopathic pulmonary fibrosis emerges as an important public health problem, there is a need to coordinate data on incidence and mortality globally. This study aims to systematically assess all available studies to investigate the global burden of disease. Medline and Embase databases were searched systematically for all population-based studies of incidence or mortality of idiopathic pulmonary fibrosis. Clinical case series and prevalence studies were excluded. The search was supplemented using the Google search engine, hand-searching of references and conference abstracts. Data were extracted independently by two authors using a pre-specified proforma, with assessment of methodological quality. 34 studies were identified, providing data from 21 countries from 1968–2012. 28 studies reported incidence data and eight reported mortality data. In studies from the year 2000 onwards, we estimated a conservative incidence range of 3–9 cases per 100 000 per year for Europe and North America. Incidence was lower in East Asia and South America. The majority of studies showed an increase in incidence over time. The incidence of idiopathic pulmonary fibrosis is increasing worldwide and rates are coming together across countries. Current data suggest incidence is similar to that of conditions such as stomach, liver, testicular and cervical cancers.