tbuckley/cabot-search huggingface dataset:
Analysis of the work rates and heart rates of association football referees.
Authors: C Catterall, T Reilly, G Atkinson, A Coldwells
Journal: British Journal of Sports Medicine (1993)

This study aimed to describe the work-rate profiles of referees during soccer matches and record heart-rate responses during these games. Using video-recordings 14 referees were observed and their heart rates during the games were monitored by short-range radio telemetry. These included 11 football league matches. The exercise intensity was largely submaximal with a change in activity every 6 s. The mean distance covered during the game was 9.44 km; a significant fall in work rate was noted in the second half (P < 0.05). The mean heart rate of 165 beats min-1 did not vary between first and second halves. The work rate and heart rate varied more between individuals than with the importance of the match, but this variation was small. It was considered that refereeing top level soccer places high physiological demands on the official. This has implications for training and fitness assessment.
A persistent unilateral lung infiltrate
Authors: G Tits, J Verschakelen, M Decramer
Journal: European Respiratory Journal (1994)

We describe the case of an intrabronchial aspirated foreign body that caused a persistent right lower lobe infiltrate. A first fibreoptic bronchoscopy demonstrated a mass with tumour-like appearance in the right bronchus intermedias, but the bronchial biopsies and the cytological smears of the bronchial aspirate failed to reveal any malignancy. During a control fibreoptic bronchoscopy, we found a chicken bone in this friable granulation tissue. It was subsequently removed with a flexible bronchofibrescope and a four-pronged forceps under topical anaesthesia.
A Novel, Voltage-Dependent Nonselective Cation Current Activated by Insulin in Guinea Pig Isolated Ventricular Myocytes
Authors: Yin Hua Zhang, Jules C. Hancox
Journal: Circulation Research (2003)

Insulin regulates cardiac metabolism and function by targeting metabolic proteins or voltage-gated ion channels. This study provides evidence for a novel, voltage-dependent, nonselective cation channel (NSCC) in the heart. Under voltage clamp at 37 degrees C and with major known conductances blocked, insulin (1 nmol/L to 1 micromol/L) activated an outwardly rectifying current (Iinsulin) in guinea pig ventricular myocytes. Iinsulin could be carried by Cs+, K+, Li+, and Na+ ions but not by NMDG+. It was inhibited by the NSCC blockers gadolinium and SKF96365 but not flufenamic acid. Iinsulin was largely blocked by the insulin receptor tyrosine kinase inhibitor HNMPA-(AM)3 and by the phospholipase C inhibitor U73122 but not by its inactive analogue U73433. Staurosporine, a potent blocker of protein kinase C, did not prevent the activation of Iinsulin. Application of an analogue of diacylglycerol, 1-oleoyl-2-acetyl-sn-glycerol, mimicked the effect of insulin. This activated an outwardly rectifying NSCC that could be carried by Cs+, K+, Li+, or Na+ and that was blocked by gadolinium but not by flufenamic acid or staurosporine. We conclude that the intracellular pathway leading to activation of this novel cardiac NSCC involves phospholipase C, is protein kinase C-independent, and may depend on direct channel activation by diacylglycerol.
Reconsidering the Paradigm of Cancer Immunotherapy by Computationally Aided Real-time Personalization
Authors: Yuri Kogan, Karin Halevi–Tobias, Moran Elishmereni, Stanimir Vuk-Pavlović, Zvia Agur
Journal: Cancer Research (2012)

Although therapeutic vaccination often induces markers of tumor-specific immunity, therapeutic responses remain rare. An improved understanding of patient-specific dynamic interactions of immunity and tumor progression, combined with personalized application of immune therapeutics would increase the efficacy of immunotherapy. Here, we developed a method to predict and enhance the individual response to immunotherapy by using personalized mathematical models, constructed in the early phase of treatment. Our approach includes an iterative real-time in-treatment evaluation of patient-specific parameters from the accruing clinical data, construction of personalized models and their validation, model-based simulation of subsequent response to ongoing therapy, and suggestion of potentially more effective patient-specific modified treatment. Using a mathematical model of prostate cancer immunotherapy, we applied our model to data obtained in a clinical investigation of an allogeneic whole-cell therapeutic prostate cancer vaccine. Personalized models for the patients who responded to treatment were derived and validated by data collected before treatment and during its early phase. Simulations, based on personalized models, suggested that an increase in vaccine dose and administration frequency would stabilize the disease in most patients. Together, our findings suggest that application of our method could facilitate development of a new paradigm for studies of in-treatment personalization of the immune agent administration regimens (P-trials), with treatment modifications restricted to an approved range, resulting in more efficacious immunotherapies.
Input impedance of the systemic circulation in man.
Authors: W W Nichols, C R Conti, W E Walker, W R Milnor
Journal: Circulation Research (1977)

To determine the systemic input impedance, pulsatile pressure and flow were measured in the ascending aorta in 16 human subjects who were undergoing diagnostic cardiac catheterization. Blood flow was measured with a catheter-tip electromagnetic velocity meter, and pressure with an external transducer connected with the fluid-filled lumen of the catheter. Five subjects were found to have no evidence of cardiovascular disease (group A, mean age 32 +/- 2 years, mean aortic pressure 97 +/- 4 mm Hg). Seven had clinical and angiographic signs of coronary arterial disease, and mean pressures less than 100 mm Hg (group B, mean age 48 +/- 2 years). Four subjects had signs of coronary disease and mean pressures greater than 100 mm Hg (group C, mean age 48 +/- 3 years). The frequency spectra of impedance were qualitatively similar in all three groups and resembled those previously observed in the canine aorta. Characteristic impedance was lower in the normal subjects (group A, average 53 dyn sec cm-5) than in the subjects with coronary artery disease (groups B and C, average 129 dyn sec cm-5). Among the subjects with coronary disease, characteristic impedance was higher in the hypertensive subjects (group C, average 202 dyn sec cm-5) than in those with lower mean pressures (group B, average 95 dyn sec cm-5). External left ventricular work per unit time (hydraulic power) averaged 1715 milliwatts (mW) in group A, 1120 mW in group B, and 2372 mW in group C. Cardiac outputs were within normal limits in all subjects, but tended to be lower in group B than in group C. These results suggest that the subjects of group C were better able to meet the increased energy demands imposed by an abnormally high aortic input impedance. Further investigation is needed to learn whether the high impedances in subjects with coronary disease represent an increase with age and transmural pressure alone, or whether some additional factor is involved. The data on relatively normal subjects permit a tentative definition of the normal limits for aortic input impedance in man: 26-80 dyn sec cm-5.
Membrane transport by murine lymphocytes. I. A rapid sampling technique as applied to the adenosine and thymidine systems.
Authors: P R Strauss, J M Sheehan, E R Kashket
Journal: The Journal of Experimental Medicine (1976)

We have developed a rapid sampling technique for animal cells in suspension for the purpose of measuring membrane transport in lymphocytes. The method involves rapid centrifugation of cells through a layer of silicone oil into perchloric acid after incubation periods as short as 4 s. Using this method we have described the uptake of thymidine and the uptake and transport systems of adenosine by murine bulk nonadherent spleen cells. The two uptake systems are markedly different. Adenosine was shown to be taken up by classical carrier-mediated diffusion, while thymidine was not. In addition we have explored the metabolism of the two nucleosides under the conditions we employed for measuring transport or uptake; Both nucleosides are phosphorylated extensively. We also investigated the uptake and metabolism of thymidine over a 2-h interval the standard time used to measure DNA synthesis in lymphocytes. Unless cells were separated from medium by centrifugation through oil before TCA addition, the TCA precipitable counts exceeded the total radioactive uptake. Hence the standard method for measuring thymidine utilization yields estimates under these conditions which can be as much as 100% too high.
Lateral bone density measurements in osteoarthritis of the lumbar spine.
Authors: D J Peacock, P Egger, P Taylor, M I Cawley, C Cooper
Journal: Annals of the Rheumatic Diseases (1996)

To investigate whether spinal osteoarthritis (OA) is responsible for the common finding that lumbar spine bone mineral density (BMD) is greater when measured in the anteroposterior plane than when measured in the lateral plane.We studied lateral spine radiographs from 63 women who attended a hospital outpatient department for bone density measurement and who also underwent lumbar spine radiography. Osteoarthritis was assessed using both the Kellgren and Lawrence scale and a scoring system for osteophytosis. Bone density was measured in the anteroposterior and lateral planes using a Hologic QDR-2000 instrument.The mean anteroposterior BMD (0.92 g/cm2) was significantly greater than the lateral BMD (0.59 g/cm2) (p < 0.01), and the difference between antero-posterior and lateral measurements was significantly associated with both increasing Kellgren and Lawrence score and osteophyte score, even after adjustment for age.These data suggest that spinal OA is a major cause of the difference between anteroposterior and lateral BMD and that lateral BMD may provide a more accurate representation of true vertebral body bone density in patients with OA of the lumbar spine.
Impact of Sex and Gonadal Steroids on Prolongation of Ventricular Repolarization and Arrhythmias Induced by <i>I</i> <sub>K</sub> -Blocking Drugs
Authors: Thai V. Pham, Eugene A. Sosunov, Ravil Z. Gainullin, Peter Danilo, Michael R. Rosen
Journal: Circulation (2001)

Background —Mechanisms for longer rate-corrected QT intervals and higher incidences of drug-induced torsade de pointes in women than in men are incompletely defined, although gonadal steroids are assumed to be important determinants of these differences. Methods and Results —We used microelectrode techniques to study isolated rabbit right ventricular endocardium from control male and female and castrated male (ORCH) and female (OVX) rabbits. Action potential duration to 30% repolarization (APD 30 ) was significantly shorter in male than female and in ORCH than OVX at a cycle length of 500 ms. The I Ks blocker chromanol 293B had no effect on APD in males or females. The I Kr blocker dofetilide prolonged APD in female and ORCH more than in male and OVX. At 10 − 6 mol/L dofetilide (cycle length=1 second), the incidence of early afterdepolarizations was: female, 67%; ORCH, 56%; male, 40%; and OVX, 28%. Serum 17β-estradiol levels were unrelated to the effects of dofetilide, but as testosterone levels increased, the dofetilide effect to increase APD diminished, as did early afterdepolarization incidence. Conclusions —Sex-related differences in basal right ventricular endocardial AP configuration persist in castrated rabbits, suggesting that extragonadal factors contribute to the differences in ventricular repolarization. In this model, drugs that block I Kr but not I Ks prolong repolarization in a way that suggests that protection from excess prolongation in males is attributable to testosterone, whereas the risk of excess prolongation of repolarization in females is related to sex-determined factors in addition to estrogen.
30-Day Mortality and Major Complications after Radical Prostatectomy: Influence of Age and Comorbidity
Authors: Shabbir M. H. Alibhai, Marc Leach, George Tomlinson, Murray D. Krahn, Neil Fleshner, Eric Holowaty, Gary Naglie
Journal: JNCI Journal of the National Cancer Institute (2005)

Radical prostatectomy is associated with excellent long-term disease control for localized prostate cancer. Prior studies have suggested an increased risk of short-term complications among older men who underwent radical prostatectomy, but these studies did not adjust for comorbidity.We examined mortality and complications occurring within 30 days following radical prostatectomy among all 11,010 men who underwent this surgery in Ontario, Canada, between 1990 and 1999 using multivariable logistic regression modeling. We adjusted for comorbidity using two common comorbidity indices. Statistical tests were two-sided.Overall, 53 men (0.5%) died, and 2195 [corrected] (19.9%[corrected]) had one or more complications within 30 days of radical prostatectomy. In models adjusted for comorbidity and year of surgery, age was associated with an increased risk of 30-day mortality (odds ratio = 2.04 per decade of age, 95% confidence interval [CI] = 1.23 to 3.39). However, the absolute 30-day mortality risk was low, even in older men, at 0.66% (95% CI = 0.2 to 1.1%) for men aged 70-79 years. In adjusted models, age was associated with an increased risk of cardiac (Ptrend < .001), respiratory (Ptrend = .01), and miscellaneous medical (Ptrend = .058) complications. Similarly, increasing comorbidity was associated with a higher risk of all categories of complications.Increasing comorbidity is a stronger predictor than age of almost all categories of early complications after radical prostatectomy. The risk of postoperative mortality after radical prostatectomy is relatively low for otherwise healthy older men up to age 79.
Hypoxia-inducible factor 2α regulates key neutrophil functions in humans, mice, and zebrafish
Authors: A. A. Roger Thompson, Philip M. Elks, Helen M. Marriott, Suttida Eamsamarng, Kathryn R. Higgins, Amy Lewis, Lynne Williams, Selina Parmar, Gary Shaw, Emmet E. McGrath, Federico Formenti, Fredericus J. Van Eeden, Vuokko L. Kinnula, Christopher W. Pugh, Ian Sabroe, David H. Dockrell, Edwin R. Chilvers, Peter A. Robbins, Melanie J. Percy, M. Celeste Simon, Randall S. Johnson, Stephen A. Renshaw, Moira K. B. Whyte, Sarah R. Walmsley
Journal: Blood (2013)
Tangiopoietins-1 and -2 are differentially regulated and make distinct contributions to synovial Tie2 activation in patients with rheumatoid arthritis and psoriatic arthritis
Authors: M Frleta, L G M van Baarsen, D de Launay, M Garrelfs, D M Gerlag, P P Tak, K A Reedquist
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> The angiogenic factors angiopoietin-1 (Ang-1) and Ang-2 are differentially expressed in the serum and synovial fluid of patients with different forms of arthritis. Ang-1 and Ang-2 contribute to inflammation and joint destruction in rheumatoid arthritis (RA), but the underlying mechanisms for their differential expression and their consequences for synovial Tie2 activation are unknown. Here the authors examined relationships between synovial expression of Ang-1 and Ang-2, and Tie2 activation in patients with RA and psoriatic arthritis (PsA), and the expression of transcription factors (TF) regulating Ang expression. <h3>Materials and methods</h3> Ang-1, Ang-2, Tie2 and phosphorylated (p) active Tie2 expression was examined by immunohistochemistry combined with digital image analysis in synovial biopsies from 20 RA and 19 PsA patients. Relationships between Ang expression and Tie2 activation were compared. <i>In silico</i> analysis was conducted to identify possible TF candidates in the Ang-1 promoter, using four different TF binding site prediction programmes. RA synovial expression of TF and Ang-1 was examined in publicly available gene expression data sets. Candidate TF were characterised by immunohistochemistry. <h3>Results</h3> Synovial Ang-1 expression was elevated approximately fourfold in patients with RA (p&lt;0.05), while Ang-2 expression was similar in RA and PsA. The ratio of Ang-1 expression to Ang-2 was increased in RA (integrated optical density±SEM, 4.87±1.02) versus PsA (0.57±0.20) (p&lt;0.001), and Ang-1 expression inversely correlated with Ang-2 expression in RA synovial tissue (r=−0.784, p&lt;0.005). Tie2 activation was enhanced in RA (0.62±0.10) compared to PsA (0.18±0.11) (p&lt;0.05), and a strong positive correlation was observed between Tie2 engagement and the ratio of Ang-1/Ang-2 expression (r=0.786, p&lt;0.01). Expression of three potential Ang-1 TF, USF-1, NF-YA and Elf-1 correlated strongly with Ang-1 expression in RA synovial tissue (p&lt;0.05) and were readily detected by immunohistochemistry. <h3>Conclusions</h3> In RA, synovial Tie2 engagement is driven primarily by enhanced local Ang-1 production. Expression of Ang-1 is differentially regulated in RA and PsA, correlating with enhanced expression of putative Ang-1 TF in RA.
Ca <sup>2+</sup> Scraps
Authors: Thomas R. Shannon, Tao Guo, Donald M. Bers
Journal: Circulation Research (2003)

Free [Ca 2+ ] inside the sarcoplasmic reticulum ([Ca 2+ ] SR ) is difficult to measure yet critically important in controlling many cellular systems. In cardiac myocytes, [Ca 2+ ] SR regulates cardiac contractility. We directly measure [Ca 2+ ] SR in intact cardiac myocytes dynamically and quantitatively during beats, with high spatial resolution. Diastolic [Ca 2+ ] SR (1 to 1.5 mmol/L) is only partially depleted (24% to 63%) during contraction. There is little temporal delay in the decline in [Ca 2+ ] SR at release junctions and between junctions, indicating rapid internal diffusion. The incomplete local Ca 2+ release shows that the inherently positive feedback of Ca 2+ -induced Ca 2+ release terminates, despite a large residual driving force. These findings place stringent novel constraints on how excitation-contraction coupling works in heart and also reveal a Ca 2+ store reserve that could in principle be a therapeutic target to enhance cardiac function in heart failure.
Prognostic value of apoptotic cells and infiltrating neutrophils in graft-versus-host disease of the gastrointestinal tract in humans: TNF and Fas expression
Authors: Gérard Socié, Jean-Yves Mary, Marc Lemann, Marjan Daneshpouy, Philippe Guardiola, Véronique Meignin, Lionel Ades, Hélène Esperou, Patricia Ribaud, Agnès Devergie, Eliane Gluckman, Jean-Claude Ameisen, Anne Janin
Journal: Blood (2003)
Paracetamol and cyclooxygenase inhibition: is there a cause for concern?
Authors: Burkhard Hinz, Kay Brune
Journal: Annals of the Rheumatic Diseases (2011)

Paracetamol is recommended as first-line therapy for pain associated with osteoarthrosis and is one of the most widely used over-the-counter analgesic drugs worldwide. Despite its extensive use, its mode of action is still unclear. Although it is commonly stated that paracetamol acts centrally, recent data imply an inhibitory effect on the activity of peripheral prostaglandin-synthesising cyclooxygenase enzymes. In this context paracetamol has been suggested to inhibit both isoforms in tissues with low levels of peroxide by reducing the higher oxidation state of cyclooxygenase enzymes. Two recent studies have also demonstrated a preferential cyclooxygenase 2 (COX-2) inhibition by paracetamol under different clinically relevant conditions. This review attempts to relate data on paracetamol's inhibitory action on peripheral cyclooxygenase enzymes to the published literature on its anti-inflammatory action and its hitherto underestimated side-effects elicited by cyclooxygenase inhibition. As a result, a pronounced COX-2 inhibition by paracetamol is expected to occur in the endothelium, possibly explaining its cardiovascular risk in epidemiological studies. A careful analysis of paracetamol's cardiovascular side-effects in randomised studies is therefore strongly advised. On the basis of epidemiological data showing an increased gastrointestinal risk of paracetamol at high doses or when co-administered with classic cyclooxygenase inhibitors, paracetamol's long-term gastrointestinal impact should be investigated in randomised trials. Finally, paracetamol's fast elimination and consequently short-lived COX-2 inhibition, which requires repetitive dosing, should be definitely considered to avoid overdosage leading to hepatotoxicity.
Poor Outcome in Estrogen Receptor–Positive Breast Cancers Predicted by Loss of <i>Plexin B1</i>
Authors: Achim Rody, Uwe Holtrich, Regine Gaetje, Mathias Gehrmann, Knut Engels, Gunter von Minckwitz, Sibylle Loibl, Raihanatou Diallo-Danebrock, Eugen Ruckhäberle, Dirk Metzler, Andre Ahr, Christine Solbach, Thomas Karn, Manfred Kaufmann
Journal: Clinical Cancer Research (2007)

Abstract Purpose: A common characteristic of mammary carcinomas is an inverse relationship between the estrogen receptor (ER) status and the proliferative activity of the tumor. Yet, a subset of ER-positive breast cancers is characterized by a high proliferation, suggesting malfunctions in ER responsiveness that influence the biological and therapeutic behavior of tumor cells. The expression of several ER-dependent genes seems to be dysregulated among those “uncoupled” tumors. One of those genes is plexin B1, a cell-surface receptor for the semaphorin Sema4D (CD 100). However, the biological role of plexin B1 in breast cancer is largely unknown. Experimental Design: Expression data of plexin B1 were obtained from Affymetrix microarray analysis of n = 119 breast cancer specimens. Validation was done by quantitative real-time PCR and protein expression was evaluated by immunohistochemistry. Expression data were compared with clinical characteristics as well as follow-up data of the disease. Results: Low plexin B1 expression levels characterize a more aggressive tumor phenotype. The expression of plexin B1 is strongly correlated with the ER status. However, even among ER-positive tumors, loss of plexin B1 is associated with an impaired prognosis of breast cancer patients in both univariate (all patients, P = 0.0062; ER positive, P = 0.0107) and multivariate analyses (all patients, P = 0.032; ER positive, P = 0.022). Immunohistochemistry reveals that the tumor cells themselves and not the endothelial cells are the major source of plexin B1 expression in the tumor. Conclusion: Plexin B1 acts not only as a new important prognostic but should also represent a predictive marker indicating an endocrine resistance. These data give a new insight in markers that could be involved in endocrine dysregulation of breast cancer.