tbuckley/cabot-search huggingface dataset:
Can patients with McArdle’s disease run?
Authors: M Pérez, M Moran, C Cardona, J L Maté-Muñoz, J C Rubio, A L Andreu, M A Martin, J Arenas, A Lucia
Journal: British Journal of Sports Medicine (2006)

Patients with McArdle’s disease commonly adopt a sedentary lifestyle. This sedentary behaviour, however, usually worsens the limited exercise capacity of these patients. Although eccentric muscle work can be associated with rhabdomyolysis, supervised eccentric training with gradually increasing loads has important advantages compared with conventional concentric work, particularly for patients with a poor cardiorespiratory system. We report the beneficial effects (particularly, increased VO 2peak (from 14.6 to 30.8 ml/kg/min) and increased gross muscle efficiency (from 13.8% to 17.2%)) induced by a supervised aerobic training programme of 7 months duration including 3–4 running sessions (⩽60 min/session) per week in a 38-year-old patient. These preliminary data suggest the potential therapeutic value of this type of exercise in these patients.
The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6.
Authors: M Peters, S Jacobs, M Ehlers, P Vollmer, J Müllberg, E Wolf, G Brem, K H Meyer zum Büschenfelde, S Rose-John
Journal: The Journal of Experimental Medicine (1996)

Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and murine target cells, but murine IL-6 on murine cells only, we constructed transgenic mice expressing the hsIL-6R. We report here that in the presence of hsIL-6R, mice are hypersensitized towards hIL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the detected acute phase response persists for a longer period of time. The IL-6/IL-6R complex prolongs markedly the Il-6 plasma half-life. Our results reinforce the role of the hsIL-6R as an agonistic protein, help to understand the function of the hsIL-6R in vivo, and highlight the significance of the receptor in the induction of the acute phase response.
Maturational arrest from CD4+8+ to CD4+8- thymocytes in a mutant strain (LEC) of rat.
Authors: T Agui, M Oka, T Yamada, T Sakai, K Izumi, Y Ishida, K Himeno, K Matsumoto
Journal: The Journal of Experimental Medicine (1990)

A mutant strain (LEC) of rats was found to have a novel defect in T cell maturation, that is, arrest of differentiation from CD4+8+ to CD4+8- but not to CD4-8+ thymocytes. FACS analyses demonstrated a deficiency in the CD4+8- T cell subset in the thymus and a marked decrease in CD4+ T cells in peripheral lymphoid organs. Expression of the T cell receptor (TCR)/CD3 complex in CD4+8+ and CD4-8+ thymocytes of LEC rats was normal. Expression of class II major histocompatibility complex (MHC) in the thymus of LEC rats was also the same as that of normal rats. These results indicate that maturational arrest occurs only in the transition pathway from CD4+8+ to CD4+8- thymocytes, and that this mutation can not be attributed to the default of expression of either TCR/CD3, CD4, or class II MHC antigen. Consequently, dysfunction of helper T cells was observed in LEC rats, while killer T cells and B cells functioned normally. Although the complete identification of the origin of this mutation requires further studies, it is hoped that such investigations will throw light on the mechanism of positive selection.
Blood Flow in Cutaneous Tissue in Man Studied by Washout of Radioactive Xenon
Authors: PER SEJRSEN
Journal: Circulation Research (1969)

Washout of 133 xenon from a local depot in cutaneous tissue has been investigated in man to develop a method for blood flow measurement in that tissue. The tissue was labeled both by injecting 133 xenon in saline solution intracutaneously and by a nontraumatic epicutaneous application technique. The initial selectivity of the labeling and the subsequent accumulation of 133 xenon in subcutaneous tissue were examined by radioautography and by a special tissue separation technique. From the observations a two-compartment clearance model is suggested by which the cutaneous blood flow can be obtained separately from that of the subcutaneous tissue. Blood flow in the cutaneous tissue in the lateral region of the leg was 5.7 (SD 1.3) ml/100 g · min at an ambient temperature of 19° to 22°C. There were variations between different skin sites.
Alternative M2 Activation of Kupffer Cells by PPARδ Ameliorates Obesity-Induced Insulin Resistance
Authors: Justin I. Odegaard, Roberto R. Ricardo-Gonzalez, Alex Red Eagle, Divya Vats, Christine R. Morel, Matthew H. Goforth, Vidya Subramanian, Lata Mukundan, Anthony W. Ferrante, Ajay Chawla
Journal: Cell Metabolism (2008)
Monocytes Control Second-Phase Neutrophil Emigration in Established Lipopolysaccharide-induced Murine Lung Injury
Authors: Kevin Dhaliwal, Emma Scholefield, David Ferenbach, Michael Gibbons, Rodger Duffin, David A. Dorward, Andrew Conway Morris, Duncan Humphries, Alison MacKinnon, Tom S. Wilkinson, William A. H. Wallace, Nico van Rooijen, Matthias Mack, Adriano G. Rossi, Donald J. Davidson, Nik Hirani, Jeremy Hughes, Chris Haslett, A. John Simpson
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Acute lung injury (ALI) is an important cause of morbidity and mortality, with no currently effective pharmacological therapies. Neutrophils have been specifically implicated in the pathogenesis of ALI, and there has been significant research into the mechanisms of early neutrophil recruitment, but those controlling the later phases of neutrophil emigration that characterize disease are poorly understood.Objectives: To determine the influence of peripheral blood monocytes (PBMs) in established ALI.Methods: In a murine model of LPS-induced ALI, three separate models of conditional monocyte ablation were used: systemic liposomal clodronate (sLC), inducible depletion using CD11b diphtheria toxin receptor (CD11b DTR) transgenic mice, and antibody-dependent ablation of CCR2hi monocytes.Measurements and Main Results: PBMs play a critical role in regulating neutrophil emigration in established murine LPS-induced lung injury. Gr1hi and Gr1lo PBM subpopulations contribute to this process. PBM depletion is associated with a significant reduction in measures of lung injury. The specificity of PBM depletion was demonstrated by replenishment studies in which the effects were reversed by systemic PBM infusion but not by systemic or local pulmonary infusion of mature macrophages or lymphocytes.Conclusions: These results suggest that PBMs, or the mechanisms by which they influence pulmonary neutrophil emigration, could represent therapeutic targets in established ALI.
Clinically Driven Diagnostic Antifungal Approach in Neutropenic Patients: A Prospective Feasibility Study
Authors: Corrado Girmenia, Alessandra Micozzi, Giuseppe Gentile, Stefania Santilli, Eva Arleo, Luisa Cardarelli, Saveria Capria, Clara Minotti, Claudio Cartoni, Simonetta Brocchieri, Vito Guerrisi, Giovanna Meloni, Robin Foà, Pietro Martino
Journal: Journal of Clinical Oncology (2009)

Preemptive strategies in neutropenic patients based on serum galactomannan (GM) -guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening.Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions.Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found.A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.
Heat shock proteins as 'danger signals' in sarcoidosis
Authors: Anna Dubaniewicz
Journal: European Respiratory Journal (2014)

Sarcoidosis (SA) is a multisystem granulomatous disease with unknown etiology. Like other autoimmunological disorders, SA develops due to a combination of genetic and non-infectious/infectious factors.  We evidenced, that the same mycobacterial heat shock proteins (Mtb-HSPs, especially HSP16, the main marker of dormant stage of (myco)bacteria), occurring in sarcoid tissues and in precipitated immune complexes (CIs), were inducing immune response dependently on different genetic background of host (HLA and non-HLA- NRAMP1,FCGRIIA,IIC,IIIA ), developing acute sarcoidosis/Lofgren syndrome, chronic SA, latent, or active TB. In the same group of SA and TB patients, we also found increased monocytes phagocytic activity, but in contrast to TB, decreased clearance of antigens/CIs by resistant to apoptosis CD14+FcγRII+FcγRIII+CR1-CR4- monocytes with their decreased production of microbicidal/degradable nitric oxide and glutation, were detected in sarcoidosis.  All these results may explain increased uptake of low-degradable microbial and non-infectious antigens by the same polymorphic pattern recognition receptors on genetically altered APC with following persistent 9danger signals9 load: microbial HSP (pathogen-associated molecular patterns-PAMPs and/or tissue damage-associated molecular patterns-DAMPs) and human HSPs (endogenous DAMPs) with their decreased clearance, antigenemia/immunocomplexemia, increased presentation to T-cells in the context of particular HLA and B-cells, bystander activation, cross-reactivity, decreased co-stimulatory molecules and regulatory T-cells expression, apoptosis, and oxidative stress, resulting in exaggerated lymphoproliferation and sarcoid granuloma formation. Funding:grant 5160/B/P01/2010/39.
DNMT inhibitors reverse a specific signature of aberrant promoter DNA methylation and associated gene silencing in AML
Authors: Kirstin Lund, John J Cole, Nathan D VanderKraats, Tony McBryan, Nikolay A Pchelintsev, William Clark, Mhairi Copland, John R Edwards, Peter D Adams
Journal: Genome biology (2014)

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are neoplastic disorders of hematopoietic stem cells. DNA methyltransferase inhibitors, 5-azacytidine and 5-aza-2′-deoxycytidine (decitabine), benefit some MDS/AML patients. However, the role of DNA methyltransferase inhibitor-induced DNA hypomethylation in regulation of gene expression in AML is unclear. We compared the effects of 5-azacytidine on DNA methylation and gene expression using whole-genome single-nucleotide bisulfite-sequencing and RNA-sequencing in OCI-AML3 cells. For data analysis, we used an approach recently developed for discovery of differential patterns of DNA methylation associated with changes in gene expression, that is tailored to single-nucleotide bisulfite-sequencing data (Washington University Interpolated Methylation Signatures). Using this approach, we find that a subset of genes upregulated by 5-azacytidine are characterized by 5-azacytidine-induced signature methylation loss flanking the transcription start site. Many of these genes show increased methylation and decreased expression in OCI-AML3 cells compared to normal hematopoietic stem and progenitor cells. Moreover, these genes are preferentially upregulated by decitabine in human primary AML blasts, and control cell proliferation, death, and development. Our approach identifies a set of genes whose methylation and silencing in AML is reversed by DNA methyltransferase inhibitors. These genes are good candidates for direct regulation by DNA methyltransferase inhibitors, and their reactivation by DNA methyltransferase inhibitors may contribute to therapeutic activity.
Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study
Authors: Luciana Annino, Maria Luce Vegna, Andrea Camera, Giorgina Specchia, Giuseppe Visani, Giuseppe Fioritoni, Felicetto Ferrara, Antonio Peta, Stefania Ciolli, Wilma Deplano, Francesco Fabbiano, Simona Sica, Francesco Di Raimondo, Nicola Cascavilla, Antonio Tabilio, Pietro Leoni, Rosangela Invernizzi, Michele Baccarani, Bruno Rotoli, Sergio Amadori, Franco Mandelli
Journal: Blood (2002)
Efficacy and safety of timolol for prevention of supraventricular tachyarrhythmias after coronary artery bypass surgery.
Authors: H D White, E M Antman, M A Glynn, J J Collins, L H Cohn, R J Shemin, P L Friedman
Journal: Circulation (1984)

Forty-one patients undergoing coronary artery bypass grafting were randomly assigned to receive prophylactic timolol or placebo, given in a double-blind fashion. beta-Adrenoceptor-blocking therapy was stopped at least one half-life before surgery. Three to 7 hr after surgery (304 +/- 56 min), 0.5 mg of timolol or placebo was given intravenously twice daily in a double-blind manner. When oral medications were resumed postoperatively, 10 mg of timolol twice daily or placebo was continued orally. Continuous electrocardiograms were recorded for 24 hr before and for 7 days after surgery with a standard cassette recorder. No patient received digoxin. Both groups were comparable for frequency of preoperative supraventricular arrhythmias, left ventricular ejection fraction, duration of cardiopulmonary bypass, aortic cross-clamp time, number of bypass grafts, and total duration of monitoring. Analysis of arrhythmias was done by hand counts, and supraventricular arrhythmias were divided into supraventricular tachycardia and atrial fibrillation and/or flutter. Timolol decreased the frequency of supraventricular tachycardia (581 episodes placebo vs 84 timolol; p less than .05) and of atrial fibrillation and/or flutter (291 episodes placebo vs five timolol; p less than .05). Timolol decreased the number of patients with severe (heart rate greater than 200 beats/min, duration greater than 50 beats) episodes of supraventricular tachycardia (four placebo vs 0 timolol; p less than .05) and also decreased the number of episodes of severe (heart rate greater than 200 beats/min, duration greater than 5 min) atrial fibrillation and/or flutter (16 placebo vs one timolol; p less than .005). There were differences in the durations of supraventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Gefitinib on Serum Epidermal Growth Factor Receptor and HER2 in Patients with Advanced Non-Small Cell Lung Cancer
Authors: Vanesa Gregorc, Giovanni Luca Ceresoli, Irene Floriani, Anna Spreafico, Katia Bruna Bencardino, Vienna Ludovini, Lorenza Pistola, Zhasmina Mihaylova, Francesca Romana Tofanetti, Massimiliano Ferraldeschi, Valter Torri, Federico Cappuzzo, Lucio Crinò, Maurizio Tonato, Eugenio Villa
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to assess serum extracellular binding domains of epidermal growth factor receptor (EGFR) and HER2 as surrogate markers of Gefitinib (Iressa, ZD1839, AstraZeneca, London, United Kingdom) activity in patients with non-small cell lung cancer. Experimental Design: Serum EGFR and HER2 levels were monitored in blood samples taken within 1 week of starting Gefitinib at day 28 and at every computed tomography scan evaluation. EGFR and HER-2 were assayed in duplicate using commercial sandwich enzyme-linked immunosorbent assay kits (Oncogene Science Bayer Corporation, Cambridge, UK). A logistic regression analysis was performed to evaluate: (1) the relationship between best overall tumor response and basal EGFR and HER2 levels, and (2) the association between best overall tumor response and the differences of EGFR and HER2 levels obtained at the best overall tumor response and at baseline. Results: Forty-six pretreated patients were evaluated, including F/M:11/35, Eastern Cooperative Oncology Group performance status 0–1/2:39/7, IIIB/IV:11/35, and adenocarcinoma/nonadenocarcinoma 29/17. Five partial responses (11%) and 14 stable disease responses (30%) were observed. Median pretreatment EGFR and HER2 were 83.3 ng/ml and 13.7 ng/ml. For baseline EGFR and HER2, the odds ratio of progression was 0.95 [95% confidence interval (CI), 0.91–0.98; P = 0.01] and 0.87 (95% CI, 0.74–1.03; P = 0.11), respectively. The difference between the best overall tumor response and basal EGFR value was predictive for response with a 6% increase in the odds of progression for an increase of 1 ng/ml (odds ratio, 1.06; 95% CI, 1.01–1.11; P = 0.009) and for progression-free survival with a hazard ratio of 1.03 (95% CI, 1.01–1.04; P = 0.003). Conclusion: Modifications of EGFR serum values during treatment seem to reflect Gefitinib activity.
Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study
Authors: T. Philipp, M. Anlauf, A. Distler, H. Holzgreve, J. Michaelis, S. Wellek
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. <b>Design:</b> Randomised multicentre trial over 48 weeks with double blind comparison of treatments. <b>Setting:</b> 48 centres in four countries. <b>Patients:</b> 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) <b>Interventions:</b> Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n=215), 25 mg atenolol (n=215), 10 mg nitrendipine (n=218), or 5 mg enalapril (n=220) once daily. If diastolic blood pressure was not reduced to &lt;90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. <b>Main outcome measure:</b> Blood pressure by means of an automatic device with repeated measurements. <b>Results:</b> After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P&lt;0.001) in the nitrendipine group (n=28). <b>Conclusions:</b> There is no evidence of superiority for antihypertensive effectiveness or tolerability of the "new" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and ß blockers. <h3>Key messages</h3> Calcium channel blockers and angiotensin converting enzyme inhibitors as initial monotherapy in the treatment of hypertension Reduction in mortality has been shown only with established ß blockers and diuretics Comparison of treatment with hydrochlorothiazide, atenolol, nitrendipine, and enalapril showed no superiority of the new drug classes Atenolol was the most effective drug, while nitrendipine showed the highest drop out rat Elderly patients respond better to hydrochlorothiazide and nitrendipine, and women better to enalapril, although in both subgroups the highest rate of response was with atenolol
Validity and reliability of the Persian version of the Movement Imagery Questionnaire 2
Authors: Mahdi Rostami Haji-Abadi, Nader Rahnama, Mahdi Sohrabi, Khalil Khayambashi
Journal: British Journal of Sports Medicine (2010)

The purpose of this study was to determine the validity and reliability of the Persian version of the Vividness of the Movement Imagery Questionnaire 2 (VMIQ-2). In the first stage validity and reliability and in the second stage concurrent validity questionnaire VMIQ-2 by a Persian version of the Movement Imagery Questionnaire revised was evaluated. In the first stage of this study, 125 male and 96 female athletes of different levels of competition and in the second stage, 20 male and 30 female athletes from the two levels of competitive and non-competitive sports were studied. For the main component analysis, factor analysis and to confirm the structure of the questionnaire varimax rotation was used. The Kronbakh α applied for measuring the reliability between subscales and the correlation method was used for determining the relationship between subscales, structure determination of validity and also to determine the validity of two simultaneous questionnaires MIQ-R and VMIQ-2. The results showed that about 47% of the questions related to the variance VMIQ were covered. Values of α coefficients for subscales of visual external and internal imagery, kinesthetic imagery and total scale, was respectively r=0.86, r=0.89, r=0.91 and r=0.95, that suggests the existence of a high reliability in the subscales and overall scale vividness of movement imagery. Regarding its validity, the results showed that this questionnaire has concurrent validity (−0.70) and acceptable convergent validity of the construction between its subscales (p&lt;0.001). It can be concluded that the Persian version of VMIQ-2 has the suitable validity and reliability.