tbuckley/cabot-search huggingface dataset:
Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction
Authors: Christophe Piot, Pierre Croisille, Patrick Staat, Hélène Thibault, Gilles Rioufol, Nathan Mewton, Rachid Elbelghiti, Thien Tri Cung, Eric Bonnefoy, Denis Angoulvant, Christophe Macia, Franck Raczka, Catherine Sportouch, Gerald Gahide, Gérard Finet, Xavier André-Fouët, Didier Revel, Gilbert Kirkorian, Jean-Pierre Monassier, Geneviève Derumeaux, Michel Ovize
Journal: New England Journal of Medicine (2008)

Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction.We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction.The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected.In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.
H-2-linked control of cytotoxic T-cell responsiveness to alphavirus infection. Presence of H-2Dk during differentiation and stimulation converts stem cells of low responder genotype to T cells of responder phenotype.
Authors: A Mullbacher, R V Blanden
Journal: The Journal of Experimental Medicine (1979)

Secondary Tc cells generated against Sindbis virus (SIN) are restricted to Dk. All other H-2K or D regions tested show low specific responsiveness. F1 hybrids between low and high responders show dominance of responsiveness but lack complementation. When BALB/c (KdIdDd) low responder fetal liver stem cells were allowed to mature in irradiated high responder recipients C3H.OH (KdIdDk) a response to Dk plus SIN could be generated with Tc cells of BALB/c origin. This result, together with the failure of complementation in the F1 hybrids, implies that the lesion of low responsiveness is in the inability of viral antigen to stimulate a Tc-cell response in association with any self H-2K or H-2D molecule (of those tested) other than H-2Dk. Hypotheses compatible with these data are discussed.
Atraumatic suppurative mediastinitis and purulent pericarditis due to Eikenella corrodens.
Authors: C C Hardy, S N Raza, B Isalska, P V Barber
Journal: Thorax (1988)

Abstract Atraumatic suppurative mediastinitis is an uncommon infection. A case with an associated purulent pericarditis caused by Eikenella corrodens is reported.
Characterization of E-selectin-deficient mice: Demonstration of overlapping function of the endothelial selectins
Authors: Mark A. Labow, Christine R. Norton, John M. Rumberger, Kathleen M. Lombard-Gillooly, David J. Shuster, Jennifer Hubbard, Robert Bertko, Polly A. Knaack, Robert W. Terry, Margaret L. Harbison, Frank Kontgen, Colin L. Stewart, Kim W. McIntyre, Peter C. Will, Daniel K. Burns, Barry A. Wolitzky
Journal: Immunity (1994)
Static postural sway, proprioception, and maximal voluntary quadriceps contraction in patients with knee osteoarthritis and normal control subjects
Authors: B S Hassan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVES</h3> To investigate whether subjects with knee osteoarthritis (OA) have reduced static postural control, knee proprioceptive acuity, and maximal voluntary contraction (MVC) of the quadriceps compared with normal controls, and to determine possible independent predictors of static postural sway. <h3>METHODS</h3> 77 subjects with symptomatic and radiographic knee OA (58 women, 19 men; mean age 63.4 years, range 36–82) and 63 controls with asymptomatic and clinically normal knees (45 women, 18 men; mean age 63 years, range 46–85) underwent assessment of static postural sway. 108 subjects (59 patients, 49 controls) also underwent assessment of knee proprioceptive activity and MVC (including calculation of quadriceps activation). In patients with knee OA knee pain, stiffness, and functional disability were assessed using the WOMAC Index. The height (m) and weight (kg) of all subjects was assessed. <h3>RESULTS</h3> Compared with controls, patients with knee OA were heavier (mean difference 15.3 kg, p&lt;0.001), had increased postural lateral sway (controls: median 2.3, interquartile (IQ) range 1.8–2.9; patients: median 4.7, IQ range 1.9–4.7, p&lt;0.001), reduced proprioceptive acuity (controls: mean 7.9, 95% CI 6.9 to 8.9; patients: mean 12.0, 95% CI 10.5 to 13.6, p&lt;0.001), weaker quadriceps strength (controls: mean 22.5, 95% CI 19.9 to 24.6; patients: mean 14.7, 95% CI 12.5 to 16.9, p&lt;0.001), and less percentage activation of quadriceps (controls: mean 87.4, 95% CI 80.7 to 94.2; patients: mean 66.0, 95% CI 58.8 to 73.2, p&lt;0.001). The significant predictors of postural sway were knee pain and the ratio of MVC/body weight. <h3>CONCLUSIONS</h3> Compared with age and sex matched controls, subjects with symptomatic knee OA have quadriceps weakness, reduced knee proprioception, and increased postural sway. Pain and muscle strength may particularly influence postural sway. The interaction between physiological, structural, and functional abnormalities in knee OA deserves further study.
A Double-Blind, Placebo-Controlled Study of the Omega-3 Fatty Acid Docosahexaenoic Acid in the Treatment of Major Depression
Authors: Lauren B Marangell, James M Martinez, Holly A Zboyan, Barbara Kertz, H Florence Seung Kim, Lucy J Puryear
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid (DHA) for the treatment of major depression. METHOD: Thirty-six depressed patients were randomly assigned to receive DHA, 2 g/day, or placebo for 6 weeks. Response was defined a priori as a ≥50% reduction in the score on the Montgomery-Åsberg Depression Rating Scale. Thirty-five participants were evaluable; 18 received DHA, and 17 received placebo. RESULTS: Response rates were 27.8% in the DHA group and 23.5% in the placebo group. The difference in response rates between groups did not reach statistical significance. CONCLUSIONS: This trial failed to show a significant effect of DHA monotherapy in subjects with major depression.
Different Effects of Antihypertensive Therapies Based on Losartan or Atenolol on Ultrasound and Biochemical Markers of Myocardial Fibrosis
Authors: Michele M. Ciulla, Roberta Paliotti, Arturo Esposito, Javier Dìez, Begoña López, Björn Dahlöf, M. Gary Nicholls, Ronald D. Smith, Leen Gilles, Fabio Magrini, Alberto Zanchetti
Journal: Circulation (2004)

In hypertensive left ventricular hypertrophy (LVH), myocardial texture is altered by a disproportionate increase in fibrosis, but there is insufficient clinical evidence whether antihypertensive therapy or individual agents can induce regression of myocardial fibrosis.We compared the effects of an angiotensin II receptor antagonist with a beta-blocker on myocardial collagen volume (assessed by echoreflectivity and serum collagen markers) in 219 hypertensive patients with echocardiographically documented LVH. Patients were allocated randomly to receive losartan 50 to 100 mg/d (n=111) or atenolol 50 to 100 mg/d (n=99) with or without hydrochlorothiazide 12.5 to 25 mg/d for 36 weeks. Echoreflectivity analysis was conducted on ultrasound tracings of the midapex septum with specifically designed and validated software. A color histogram of reflecting echoes was obtained, and its spread (broadband [BB], previously shown to correlate directly with collagen volume fraction on endomyocardial biopsies) was used as the primary outcome measure. Mean color scale and serum markers of collagen synthesis (PIP, PIIIP) or degradation (CITP) were secondary outcome variables. Echoreflectivity analysis proved feasible in 106 patients (losartan 52, atenolol 54). Losartan reduced BB over 36 weeks (from 114.5 to 104.3 color levels, P<0.02), whereas atenolol treatment was associated with an increase in BB (from 109.0 to 113.6 color levels, P=NS), the difference between treatments being -12.8 color levels (95% CI -23.6 to -2.0, P=0.02). Secondary end points (mean color scale and collagen markers) also changed in the direction of decreased collagen in patients receiving losartan, but differences between groups were not statistically significant.In hypertensive patients with LVH, losartan decreases myocardial collagen content, whereas atenolol does not. The difference between the 2 treatments is statistically significant.
MicroRNA-100 Regulates Neovascularization by Suppression of Mammalian Target of Rapamycin in Endothelial and Vascular Smooth Muscle Cells
Authors: Sebastian Grundmann, Felix P. Hans, Sheena Kinniry, Jennifer Heinke, Thomas Helbing, Franziska Bluhm, Joost P.G. Sluijter, Imo Hoefer, Gerard Pasterkamp, Christoph Bode, Martin Moser
Journal: Circulation (2011)

Background— The adaptive growth of blood vessels is an important protective mechanism in cardiovascular disease. However, the underlying regulatory mechanisms of this process are only partly understood. Recently, small endogenous RNAs (microRNAs [miRNAs]) were found to play an important role in embryonic and postnatal vascular development. Here, we used miRNA transcriptome analysis after induction of hind-limb ischemia in mice to screen for miRNAs involved in adaptive blood vessel growth following arterial occlusion. Methods and Results— Using miRNA arrays, we explored the miRNA expression profile during adaptive neovascularization. We describe specific changes in miRNA expression patterns and show that miRNA-100 is significantly downregulated after induction of hind-limb ischemia in mice. Our data demonstrate that miR-100 modulates proliferation, tube formation, and sprouting activity of endothelial cells and migration of vascular smooth muscle cells and functions as an endogenous repressor of the serine/threonine protein kinase mammalian target of rapamycin (mTOR). Whereas miR-100 inhibition increased mTOR levels in endothelial cells, overexpression of miR-100 reduced mTOR expression and consequently attenuated cellular proliferation. Supporting this notion, overexpression of an mTOR construct lacking the miRNA binding site rescued the inhibitory effect of miR-100 on cell proliferation. Accordingly, miR-100 inhibition by specific antagomirs in vivo stimulated angiogenesis and resulted in functional improvement of perfusion after femoral artery occlusion in mice. In contrast, treatment with the mTOR inhibitor rapamycin had the opposite effect. Conclusions— Our data demonstrate that miR-100 has an antiangiogenic function and represses mTOR signaling in endothelial and vascular smooth muscle cells. Inhibition of miR-100 could be a novel approach for the modulation of blood vessel growth and other mTOR-dependent processes.
Tiotropium attenuates IL-13-induced goblet cell metaplasia of human airway epithelial cells
Authors: L. E. M. Kistemaker, P. S. Hiemstra, I. S. T. Bos, S. Bouwman, M. van den Berge, M. N. Hylkema, H. Meurs, H. A. M. Kerstjens, R. Gosens
Journal: Thorax (2015)

<h3>Background</h3> It has been shown that acetylcholine is both a neurotransmitter and acts as a local mediator, produced by airway cells including epithelial cells. In vivo studies have demonstrated an indirect role for acetylcholine in epithelial cell differentiation. Here, we aimed to investigate direct effects of endogenous non-neuronal acetylcholine on epithelial cell differentiation. <h3>Methods</h3> Human airway epithelial cells from healthy donors were cultured at an air–liquid interface (ALI). Cells were exposed to the muscarinic antagonist tiotropium (10 nM), interleukin (IL)-13 (1, 2 and 5 ng/mL), or a combination of IL-13 and tiotropium, during or after differentiation at the ALI. <h3>Results</h3> Human airway epithelial cells expressed all components of the non-neuronal cholinergic system, suggesting acetylcholine production. Tiotropium had no effects on epithelial cell differentiation after air exposure. Differentiation into goblet cells was barely induced after air exposure. Therefore, IL-13 (1 ng/mL) was used to induce goblet cell metaplasia. IL-13 induced MUC5AC-positive cells (5-fold) and goblet cells (14-fold), as assessed by histochemistry, and MUC5AC gene expression (105-fold). These effects were partly prevented by tiotropium (47–92%). Goblet cell metaplasia was induced by IL-13 in a dose-dependent manner, which was inhibited by tiotropium. In addition, tiotropium reversed goblet cell metaplasia induced by 2 weeks of IL-13 exposure. IL-13 decreased forkhead box protein A2 (FoxA2) expression (1.6-fold) and increased FoxA3 (3.6-fold) and SAM-pointed domain-containing ETS transcription factor (SPDEF) (5.2-fold) expression. Tiotropium prevented the effects on FoxA2 and FoxA3, but not on SPDEF. <h3>Conclusions</h3> We demonstrate that tiotropium has no effects on epithelial cell differentiation after air exposure, but inhibits and reverses IL-13-induced goblet cell metaplasia, possibly via FoxA2 and FoxA3. This indicates that non-neuronal acetylcholine contributes to goblet cell differentiation by a direct effect on epithelial cells.
The genetics of systemic lupus erythematosus and implications for targeted therapy
Authors: A. L. Sestak, B. G. Furnrohr, J. B. Harley, J. T. Merrill, B. Namjou
Journal: Annals of the Rheumatic Diseases (2011)

Observations of familial aggregation (λs=8–29) and a 40% identical twin concordance rate prompted recent work towards a comprehensive genetic analysis of systemic lupus erythematosus (SLE). Since 2007, the number of genetic effects known to be associated with human lupus has increased by fivefold, underscoring the complexity of inheritance that probably contributes to this disease. Approximately 35 genes associated with lupus have either been replicated in multiple samples or are near the threshold for genome-wide significance (p&gt;5×10<sup>−8</sup>). Some are rare variants that convincingly contribute to lupus only in specific subgroups. Strong associations have been found with a large haplotype block in the human leucocyte antigen region, with Fcγ receptors, and with genes coding for complement components, in which a single gene deletion may cause SLE in rare familial cases and copy number variation is more common in the larger population of SLE patients. Examples of newly discovered genes include <i>ITGAM</i>, <i>STAT4</i> and <i>MECP2</i>/<i>IRAK1</i>. Ongoing studies to build models in which combinations of associated genes might contribute to specific disease manifestations should contribute to improved understanding of disease pathology. In addition, pharmacogenomic components of ongoing clinical trials are likely to provide insights into fundamental disease pathology as well as contributing to informed patient selection for targeted treatments and biomarkers to guide dosing and gauge responsiveness. Besides these potentially valuable new insights into the pathophysiology of an enigmatic, potentially deadly, and, as yet, unsolved disease, genetic studies are likely to suggest novel molecular targets for strategic development of safer and more effective therapeutics.
Anatomic causes of pulmonary stenosis in complete transposition.
Authors: S Shrivastava, S M Tadavarthy, T Fukuda, J E Edwards
Journal: Circulation (1976)

Among 166 specimens with classical complete transposition, pulmonary or subpulmonary stenosis was present in 22 cases. The bases for obstruction were pulmonary valvular stenosis (one case), membranous subpulmonary stenosis (nine cases), anomalous attachment of the mitral valve to the ventricular septum (five cases) and combinations of causes (seven cases). Conditions contributing to combinations of causes included the above, in addition to accessory mitral or pulmonary valvular tissue and herniation of a tricuspid valvular pouch through a related ventricular septal defect. In addition to the 166 cases mentioned, our collection contained six cases of atypical complete transposition characterized by a conus being present in the each ventricel. In three of these six, subpulmonary stenosis was present and caused by a narrow inlet to the left ventricular conus.
The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: results of an Italian multicentre study
Authors: Luca Quartuccio, Martina Fabris, Elena Pontarini, Sara Salvin, Alen Zabotti, Maurizio Benucci, Mariangela Manfredi, Domenico Biasi, Viviana Ravagnani, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Pia Morassi, Fabio Fischetti, Paola Tomietto, Laura Bazzichi, Marta Saracco, Raffaele Pellerito, Marco Cimmino, Franco Schiavon, Valeria Carraro, Angelo Semeraro, Roberto Caporali, Lorenzo Cavagna, Roberto Bortolotti, Giuseppe Paolazzi, Marcello Govoni, Stefano Bombardieri, Salvatore De Vita
Journal: Annals of the Rheumatic Diseases (2013)

The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response.The study analysed 212 RA patients. European League Against Rheumatism (EULAR) response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing.The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 (response in 34/38 (89.5%) VV vs 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01), but not at month +4 (response in 32/37 (86.5%) VV vs 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09). Loss of response was observed only in VF and FF carriers ((VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)). Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anticyclic citrullinated peptide antibodies, previous treatment with ≤ 1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95% CI 4.1 to 15.1).The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Patient genotyping may be helpful to plan RTX treatment, and may be integrated with clinical predictors.
In vivo tracking of tau pathology using positron emission tomography (PET) molecular imaging in small animals
Authors: Eduardo Rigon Zimmer, Antoine Leuzy, Venkat Bhat, Serge Gauthier, Pedro Rosa-Neto
Journal: Translational Neurodegeneration (2014)

Hyperphosphorylation of the tau protein leading to the formation of neurofibrillary tangles (NFTs) is a common feature in a wide range of neurodegenerative diseases known as tauopathies, which include Alzheimer's disease (AD) and the frontotemporal dementias (FTDs). Although heavily investigated, the mechanisms underlying the pathogenesis and progression of tauopathies have yet to be fully understood. In this context, several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology, aiming to achieve a better understanding of the link between tau and neurodegeneration. To date, behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid (CSF) sampling or post-mortem analysis. Recently, several novel positron emission tomography (PET) radiopharmaceuticals targeting tau tangles have been developed, allowing for non-invasive in vivo quantification of tau pathology. Combined with tau transgenic models and microPET, these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD tauopathies. In this review, we briefly describe some of the most important insights for understanding the biological basis of tau pathology, and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.
Oral Androstenedione Administration and Serum Testosterone Concentrations in Young Men
Authors: Benjamin Z. Leder
Journal: JAMA (2000)

ContextAndrostenedione, a steroid hormone and the major precursor to testosterone, is available without prescription and is purported to increase strength and athletic performance. The hormonal effects of androstenedione, however, are unknown.ObjectiveTo determine if oral administration of androstenedione increases serum testosterone levels in healthy men.DesignOpen-label randomized controlled trial conducted between October 1998 and April 1999.SettingGeneral clinical research center of a tertiary-care, university-affiliated hospital.ParticipantsForty-two healthy men aged 20 to 40 years.InterventionSubjects were randomized to receive oral androstenedione (either 100 mg/d [n = 15] or 300 mg/d [n = 14]) or no androstenedione (n = 13) for 7 days.Main Outcome MeasuresChanges in serum testosterone, androstenedione, estrone, and estradiol levels, measured by frequent blood sampling, compared among the 3 treatment groups.ResultsMean (SE) changes in the area under the curve (AUC) for serum testosterone concentrations were −2% (7%), −4% (4%), and 34% (14%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in testosterone AUC was significant for the 300-mg/d group (P&lt;.001) but not for the 100-mg/d group (P = .48). Baseline testosterone levels, drawn 24 hours after androstenedione administration, did not change. Mean (SE) changes in the AUC for serum estradiol concentrations were 4% (6%), 42% (12%), and 128% (24%) in the groups receiving 0, 100, and 300 mg/d of androstenedione, respectively. When compared with the control group, the change in the estradiol AUC was significant for both the 300-mg/d (P&lt;.001) and 100-mg/d (P = .002) groups. There was marked variability in individual responses for all measured sex steroids.ConclusionsOur data suggest that oral androstenedione, when given in dosages of 300 mg/d, increases serum testosterone and estradiol concentrations in some healthy men.