tbuckley/cabot-search huggingface dataset:
Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis
Authors: S Van Doornum
Journal: Annals of the Rheumatic Diseases (2004)

Chronic systemic inflammation may contribute to accelerated atherosclerosis and increased arterial stiffness in patients with rheumatoid arthritis (RA). In addition to lowering cholesterol, statins have immunomodulatory effects which may be especially beneficial in patients with RA who have systemic immune activation.To investigate the effect of atorvastatin on the augmentation index (AIx: a measure of arterial stiffness) and systemic inflammation in RA.29 patients with RA (mean (SD) age 55 (13) years) with moderately active disease of long duration were studied. AIx, lipid levels, serum inflammatory markers, and disease activity score were measured before and after 12 weeks of atorvastatin 20 mg daily.AIx improved significantly from 34.1 (11.6)% to 29.9 (11)% (p = 0.0002), with the greatest improvements in AIx occurring in those subjects with the highest disease activity scores (r = -0.5, p = 0.007). Total and LDL cholesterol were reduced from 5.5 (0.9) to 3.9 (0.7) mmol/l and 3.3 (0.8) to 1.9 (0.6) mmol/l, respectively (p = 0.0001). Serum inflammatory markers remained unchanged during the study.Atorvastatin significantly reduced arterial stiffness in patients with RA. The greatest improvements were seen in patients with more active disease, suggesting that, in addition to the beneficial effects of cholesterol reduction, immune modulation may contribute to the cardioprotective effect of statins.
Funky treatments in elite sports people: do they just buy rehabilitation time?
Authors: Jill Cook
Journal: British Journal of Sports Medicine (2009)

Evidence-based treatments exist for many sports injuries; for example, reconstruction of the anterior cruciate ligament (ACL) is clinically effective and has evidence to support it. Other injuries that have a more difficult, recurrent or variable time course to recovery, for example, muscle strains, tendon injuries and bone stress, have more limited evidence.

Although a range of interventions exist for these problematic conditions in ‘conventional’ or ‘mainstream’ medicine, a plethora of gurus offer more exotic interventions and ‘promise’ quicker and better outcomes and return to sport. Gurus are successful in gathering clients for their interventions in a range of ways, but one ingredient is expectation. There is a wealth of information that shows clinical enthusiasm (‘Gee, he’s confident'), novelty (‘No one told me about this!’) and expense (‘The best money can buy’) relate to improved outcomes—usually by increasing expectation1—this is …
THE ETIOLOGY OF AORTIC REGURGITATION
Authors: A. K. Gordon
Journal: BMJ (1919)

SiR,-Dr.Tlleodore Fishier does not now deny that endo- carditis is a common occurrence in the course of an attack of sacsriet ever, bat aserts, without bringing forward any evidence in support of his ontention, that it must be caused, not by the sarlet fever, bu:t by one or other of its complications.This is a question, as it sems to me, simply of nornmemelature, and is certainly of no practical importance.
Plasma elevation of stromal cell–derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells
Authors: Koichi Hattori, Beate Heissig, Kei Tashiro, Tasuku Honjo, Masatoshi Tateno, Jae-Hung Shieh, Neil R. Hackett, Mannix S. Quitoriano, Ronald G. Crystal, Shahin Rafii, Malcolm A. S. Moore
Journal: Blood (2001)
cAMP Regulates Cell Proliferation and Cyst Formation in Autosomal Polycystic Kidney Disease Cells
Authors: KAZUSHIGE HANAOKA, WILLIAM B. GUGGINO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Both epithelial cell proliferation and fluid accumulation are responsible for cyst growth in autosomal dominant polycystic kidney disease (ADPKD). It was previously reported that the cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in cysts from ADPKD patients and suggested that cAMP-stimulated Cl - and fluid secretion occurs through CFTR. The purpose of this study was to investigate the role of cell proliferation in cyst formation in ADPKD and to explore further the role of fluid secretion in cyst growth. Primary cultures both of ADPKD epithelial cells and a mixed population of normal renal epithelial cells isolated from the cortex (HRCE cells) were used. This study tested whether cAMP was involved both in stimulating cell proliferation and formation of cysts in vitro . 3 H-Thymidine incorporation assays showed that epidermal growth factor stimulated proliferation both in ADPKD cells and HRCE cells. In addition, cAMP stimulated DNA synthesis and cell proliferation in ADPKD, but not HRCE, cells. The effects of cAMP and epidermal growth factor on cell growth in ADPKD cells were additive. cAMP also stimulated cyst enlargement and fluid secretion in ADPKD cells. By contrast, cyst formation and enlargement from HRCE cells occurred without cAMP. Fluid secretion into the cyst lumen was blocked by diphenylamine carboxylic acid (DPC) and glibenclamide in ADPKD cells but blocked only by DPC in HRCE cells. This study showed that ADPKD cells have unique characteristics; cAMP stimulates fluid secretion and cell proliferation, indicating cAMP plays a very important role in cyst growth during the course of ADPKD.
DOUBLE-BLIND RANDOMISED TRIAL OF INTRAVENOUS TISSUE-TYPE PLASMINOGEN ACTIVATOR VERSUS PLACEBO IN ACUTE MYOCARDIAL INFARCTION
Authors: M. Verstraete, R.W. Brower, D. Collen, A.J. Dunning, J. Lubsen, P.L. Michel, J. Schofer, J. Vanhaecke, F. Van De Werf, W. Bleifeld, B. Charbonnier, D.P. De Bono, R.J. Lennane, D.G. Mathey, PH. Raynaud, A. Vahanian, G.A.vande Kley, R.Von Essen
Journal: The Lancet (1985)
Effect of Discontinuation of Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease
Authors: Paul van der Valk, Evelyn Monninkhof, Job van der Palen, Gerhard Zielhuis, Cees van Herwaarden
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The aim of this double-blind single center study (the COPE study) was to investigate the effect of discontinuation of the inhaled corticosteroid fluticasone propionate (FP) on exacerbations and health-related quality of life in patients with chronic obstructive pulmonary disease. After 4 months of treatment with FP (1,000 microg/day), 244 patients were randomized to either continue FP or to receive placebo for 6 months: 123 patients continued FP (FP group), and 121 received placebo (placebo group). In the FP group, 58 (47%) patients developed at least one exacerbation compared with 69 (57%) in the placebo group. The hazard ratio of a first exacerbation in the placebo group compared with the FP group was 1.5 (95% confidence interval [CI] 1.1-2.1). In the placebo group 26 patients (21.5%) experienced rapid recurrent exacerbations and were subsequently unblinded and prescribed FP compared with 6 patients (4.9%) in the FP group (relative risk = 4.4; 95% CI 1.9-10.3). Over a 6-month period, a significant difference in favor of the FP group was observed in the total score (+2.48 95% CI 0.37-4.58), activity domain (+4.64 95% CI 1.60-7.68), and symptom domain (+4.58 95% CI 1.05-8.10) of the St. George's Respiratory Questionnaire. This study indicates that discontinuation of FP in patients with chronic obstructive pulmonary disease is associated with a more rapid onset and higher recurrence-risk of exacerbations and a significant deterioration in aspects of Health-Related Quality of Life.
Hereditary dysplastic nevus syndrome: lymphoid cell ultraviolet hypermutability in association with increased melanoma susceptibility.
Authors: Mohan I. R. Perera, Kyung Um, Mark H. Greene, Haywood L. Waters, Anders Bredberg, Kenneth H. Kraemer
Journal: Cancer Research (1986)

The hereditary dysplastic nevus syndrome (DNS) is a well-characterized disorder in which affected individuals have increased numbers of premalignant (dysplastic) nevi and a markedly increased risk of developing cutaneous melanoma. Seeking evidence of a systemic disorder in DNS, we examined the effect of ultraviolet radiation on cultured lymphoid cells. Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with hereditary DNS had similar survival values following treatment with 2.3 to 9.0 J of 254-nm ultraviolet radiation per m2 as did lines from control individuals. Mutagenesis at the hypoxanthineguanine phosphoribosyltransferase locus was assessed by measuring the induction of resistance to thioguanine using a microtiter well assay. Three lymphoblastoid cell lines from patients with hereditary DNS and melanoma had a 2- to 3-fold greater frequency of induced mutants per clonable cell than three normal lines following exposure to 4.5 to 9.0 J of ultraviolet radiation per m2. Expanded clones of mutated DNS lymphoblastoid cell lines had less than 6% of normal hypoxanthine-guanine phosphoribosyltransferase activity. Inhibition and recovery of DNA synthesis following ultraviolet exposure were similar in 2 DNS and 2 normal lines. Repair by DNS lines of ultraviolet-induced DNA damage was in the normal range as measured by alkaline elution. Thus, hereditary DNS exhibits in vitro hypermutability which may reflect increased susceptibility to ultraviolet-induced somatic mutations in vivo. This abnormality may be related to the increased melanoma susceptibility of patients with hereditary DNS.
Binding of CD40L to Mac-1's I-Domain Involves the EQLKKSKTL Motif and Mediates Leukocyte Recruitment and Atherosclerosis—But Does Not Affect Immunity and Thrombosis in Mice
Authors: Dennis Wolf, Jan-David Hohmann, Ansgar Wiedemann, Kamila Bledzka, Hermann Blankenbach, Timoteo Marchini, Katharina Gutte, Katharina Zeschky, Nicole Bassler, Natalie Hoppe, Alexandra Ortiz Rodriguez, Nadine Herr, Ingo Hilgendorf, Peter Stachon, Florian Willecke, Daniel Duerschmied, Constantin von zur Muhlen, Dmitry A. Soloviev, Li Zhang, Christoph Bode, Edward F. Plow, Peter Libby, Karlheinz Peter, Andreas Zirlik
Journal: Circulation Research (2011)

Rationale: CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and hemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective: Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results: CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affinity interaction was revealed by surface-plasmon-resonance analysis. We identified the motif EQLKKSKTL, an exposed loop between the α1 helix and the β-sheet B, on Mac-1 as binding site for CD40L. A linear peptide mimicking this sequence, M7, specifically inhibited the interaction of CD40L and Mac-1. A cyclisized version optimized for in vivo use, cM7, decreased peritoneal inflammation and inflammatory cell recruitment in vivo. Finally, LDLr −/− mice treated with intraperitoneal injections of cM7 developed smaller, less inflamed atherosclerotic lesions featuring characteristics of stability. However, cM7 did not interfere with CD40L-CD40 binding in vitro and CD40L-GPIIb/IIIa-mediated thrombus formation in vivo. Conclusions: We present the novel finding that CD40L binds to the EQLKKSKTL motif on Mac-1 mediating leukocyte recruitment and atherogenesis. Specific inhibition of CD40L-Mac-1 binding may represent an attractive anti-inflammatory treatment strategy for atherosclerosis and other inflammatory conditions, potentially avoiding the unwanted immunologic and thrombotic effects of global inhibition of CD40L.
All-age relationship between arm span and height in different ethnic groups
Authors: Philip H. Quanjer, André Capderou, Mumtaz M. Mazicioglu, Ashutosh N. Aggarwal, Sudip Datta Banik, Stevo Popovic, Francis A.K. Tayie, Mohammad Golshan, Mary S.M. Ip, Marc Zelter
Journal: European Respiratory Journal (2014)

The objective of the present study was to establish multiethnic, all-age prediction equations for estimating stature from arm span in males and females. The arm span/height ratio (ASHR) from 13 947 subjects (40.9% females), aged 5–99 years, from nine centres (in China, Europe, Ghana, India and Iran) was used to predict ASHR as a function of age using the lambda, mu and sigma method. Z-scores for forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and FEV 1 /FVC in 1503 patients were calculated using measured height and height calculated from arm span and age. ASHR varied nonlinearly with age, was higher in males than in females and differed significantly between the nine sites. The data clustered into four groups: Asia, Europe, Ghana and Iran. Average predicted FEV 1 , FVC and FEV 1 /FVC using measured or predicted height did not differ, with standard deviations of 4.6% for FEV 1 , 5.0% for FVC and 0.3% for FEV 1 /FVC. The percentages of disparate findings for a low FEV 1 , FVC and FEV 1 /FVC in patients, calculated using measured or predicted height, were 4.2%, 3.2% and 0.4%, respectively; for a restrictive pattern, there were 1.0% disparate findings. Group- and sex-specific equations for estimating height from arm span and age to derive predicted values for spirometry are clinically useful.
Integrin-mediated collagen gel contraction by cardiac fibroblasts. Effects of angiotensin II.
Authors: M L Burgess, W E Carver, L Terracio, S P Wilson, M A Wilson, T K Borg
Journal: Circulation Research (1994)

Angiotensin II (Ang II), a vasoactive octapeptide, has been implicated in cardiac growth and the development of hypertrophy and fibrosis secondary in hypertensive disease. These consequences of Ang II imply an effect on the function and morphology of cardiac interstitial cells (fibroblasts). The present investigation was designed to (1) determine whether neonatal heart fibroblasts (NHFs) possess functional Ang II receptors on their plasma membrane and (2) examine the effects of Ang II on NHFs in vitro using three- and two-dimensional (3D and 2D, respectively) cultures. Several analytic techniques were used to test the specific questions of the present study. Since cardiac fibroblast phenotype can be influenced by culture conditions, both 2D and 3D cultures were used in the present investigations. Reverse-transcriptase polymerase chain reaction and radioligand binding analysis were used to test for the presence of Ang II receptors on NHFs. Both revealed that NHFs in 2D culture possess Ang II receptor mRNA and Ang II receptors. When isolated NHFs were cultured in 3D collagen gels and treated with Ang II, gel contraction was stimulated by NHFs. This effect was attenuated by the specific Ang II receptor antagonist [Sar1,Ala8]Ang II. Ang II-stimulated gel contraction was completely inhibited by extracellular matrix receptor (beta 1-integrin) antibodies (P &lt; .05), supporting previous studies indicating that collagen gel contraction is mediated via the integrins. Immunofluorescent staining was used to test the localization of cell-surface integrins. A more intense staining pattern for beta 1-integrin in Ang II-treated versus control cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Coaches' perspectives on implementing an evidence-informed injury prevention programme in junior community netball
Authors: N Saunders, L Otago, M Romiti, A Donaldson, P White, CF Finch
Journal: British Journal of Sports Medicine (2010)

Objective For effective sports injury prevention, information is needed about the implementation context for interventions. This study describes coaches' feedback on the implementation of an evidence-informed injury prevention programme in community junior netball using coaches' perceptions and the RE–AIM framework. Methods A lower-limb injury prevention programme (Down to Earth; D2E), for teaching safe-landing techniques, was delivered to 31 coaches from 31 junior community netball teams in a 1-h workshop. Coaches then delivered a 6-week programme at team training sessions starting in the week before the competition season commenced. 65% of coaches completed a feedback survey 17 weeks after they had delivered the programme. Results Most (88%) coaches believed that D2E improved their players' ability to perform correct landing techniques in games and that players had retained these improvements over the season. The majority (83%) indicated that an improvement in player athletic attributes was the greatest advantage of D2E, followed by a reduction in injury risk. Identified barriers to implementing D2E were running out of time and very young players finding the drills too difficult. Coaches reported that they needed more ideas for training drills that could be incorporated into their programmes and believed that their own coaching training did not adequately prepare them to implement an injury prevention programme. Conclusions Although coaches believed that D2E was effective in developing correct landing techniques, some modifications are needed to make it more suitable for younger players and coach education by accreditation courses could be improved to support the implementation of injury prevention programmes.
Long-term clinical efficacy in grass pollen–induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet
Authors: Stephen R. Durham, Waltraud Emminger, Alexander Kapp, Giselda Colombo, Jan G.R. de Monchy, Sabina Rak, Glenis K. Scadding, Jens S. Andersen, Bente Riis, Ronald Dahl
Journal: Journal of Allergy and Clinical Immunology (2010)
What survival benefits do premenopausal patients with early breast cancer need to make endocrine therapy worthwhile?
Authors: Belinda Thewes, Bettina Meiser, Vlatka M Duric, Martin R Stockler, Alan Taylor, Robin Stuart-Harris, Matthew Links, Nicholas Wilcken, Sue Anne McLachlan, Kelly-Anne Phillips, Jane Beith, Frances Boyle, Michael L Friedlander
Journal: The Lancet Oncology (2005)
Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors
Authors: J.-C. Soria, F.A. Shepherd, J.-Y. Douillard, J. Wolf, G. Giaccone, L. Crino, F. Cappuzzo, S. Sharma, S.H. Gross, S. Dimitrijevic, L. Di Scala, H. Gardner, L. Nogova, V. Papadimitrakopoulou
Journal: Annals of Oncology (2009)
Urine mutagenicity as an indicator of exposure to dietary mutagens formed during cooking of foods.
Authors: R S Baker, I Darnton-Hill, A M Bonin, A Arlauskas, C Braithwaite, M Wootton, A S Truswell
Journal: Environmental Health Perspectives (1986)

Studies were undertaken with individuals fed fried bacon meals to determine whether fruit or vegetables, ingested along with bacon, modified uptake and subsequent excretion of bacon mutagen(s). Urinary mutagenic activity was significant in those who had consumed bacon or mixed bacon/vegetable or bacon/fruit meals within the previous 2 to 3 hr period. Although urine activity varied by a factor of 4 among 15 subjects who consumed different meals, there was no evidence from this investigation that fruit or vegetables contributed to the inherent variability in total urinary mutagenic activity. However, some differences in excretion kinetics may be attributable to vegetable or fruit supplements in mixed meals.
Transient Association of the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Subunits p47phox and p67phox With Phagosomes in Neutrophils From Patients With X-Linked Chronic Granulomatous Disease
Authors: Lee-Ann H. Allen, Frank R. DeLeo, Annabelle Gallois, Satoshi Toyoshima, Kensuke Suzuki, William M. Nauseef
Journal: Blood (1999)
Evolutionary Diversification of the Sm Family of RNA-Associated Proteins
Authors: Douglas G. Scofield, Michael Lynch
Journal: Molecular Biology and Evolution (2008)

The Sm family of proteins is closely associated with RNA metabolism throughout all life. These proteins form homomorphic and heteromorphic rings consisting of six or seven subunits with a characteristic central pore, the presence of which is critical for binding U-rich regions of single-stranded RNA. Eubacteria and Archaea typically carry one or two forms of Sm proteins and assemble one homomorphic ring per Sm protein. Eukaryotes typically carry 16 or more Sm proteins that assemble to form heteromorphic rings which lie at the center of a number of critical RNA-associated small nuclear ribonucleoproteins (snRNPs). High Sm protein diversity and heteromorphic Sm rings are features stretching back to the origin of eukaryotes; very deep phylogenetic divisions among existing Sm proteins indicate simultaneous evolution across essentially all existing eukaryotic life. Two basic forms of heteromorphic Sm rings are found in eukaryotes. Fixed Sm rings are highly stable and static and are assembled around an RNA cofactor. Flexible Sm rings also stabilize and chaperone RNA but assemble in the absence of an RNA substrate and, more significantly, associate with and dissociate from RNA substrates more freely than fixed rings. This suggests that the conformation of flexible Sm rings might be modified in some specific manner to facilitate association and dissociation with RNA. Diversification of eukaryotic Sm proteins may have been initiated by gene transfers and/or genome clashes that accompanied the origin of the eukaryotic cell itself, with further diversification driven by a greater need for steric specificity within increasingly complex snRNPs.
The Genetics of Neuropsychiatric Diseases: Looking In and Beyond the Exome
Authors: Erin L. Heinzen, Benjamin M. Neale, Stephen F. Traynelis, Andrew S. Allen, David B. Goldstein
Journal: Annual Review of Neuroscience (2015)

Next-generation sequencing, which allows genome-wide detection of rare and de novo mutations, is transforming neuropsychiatric disease genetics through identifying on an unprecedented scale genes and protein-coding mutations that confer risk. Although understanding how regulatory variants influence risk remains a challenge, we are likely transitioning into a phase of neuropsychiatric disease genetics in which the rate-limiting step may no longer be gene discovery. Instead, the future will concentrate more on the biological and clinical translation of the torrent of specific risk mutations identified through next-generation sequencing. Here, we review the recent progress that resulted specifically from exome sequencing and emphasize the need for rigorous statistical evaluation of the expanding data sets, as well as expanded functional analysis of implicated proteins and mutations. Then, we introduce some of the expected opportunities and challenges investigators face when moving beyond the exome. Finally, we briefly highlight the challenge of deriving translational benefit from the progress in genetics.