tbuckley/cabot-search huggingface dataset:
Superoxide dismutase conjugated to polyethylene glycol provides sustained protection against myocardial ischemia/reperfusion injury in canine heart.
Authors: Y Tamura, L G Chi, E M Driscoll, P T Hoff, B A Freeman, K P Gallagher, B R Lucchesi
Journal: Circulation Research (1988)

Disagreement regarding the cardioprotective role of superoxide dismutase may relate to the use of different durations for induction of ischemic injury and reperfusion. The present study employed superoxide dismutase conjugated to polyethylene glycol (PEG-SOD), which has a half-life greater than 30 hours. Two protocols differing in the mode of administration and the duration of the reperfusion interval were used. Dogs were subjected to occlusion of the circumflex coronary artery for 90 minutes, then reperfused for 6 hours (Protocol A) or 4 days (Protocol B). The dogs received either polyethylene glycol conjugated to albumin (PEG-ALB) or PEG-SOD (1,000 U/kg). In Protocol A, treatment was administered starting 15 minutes before coronary occlusion and continued for 2 hours, terminating 15 minutes after reperfusion. Infarct size was determined 6 hours later. In Protocol B, the conjugated proteins were given 15 minutes before reperfusion and ended simultaneously with reperfusion. Infarct size was measured after 4 days. Infarct size (percentage of area at risk) in control (n = 9) and treated (n = 9) dogs in Protocol A differed between groups: 46.7 +/- 3.5% versus 28.3 +/- 2.9%, respectively (p less than or equal to 0.005); risk regions did not differ: 42.8 +/- 1.5% versus 43.8 +/- 2.1%, respectively. Myocardial salvage also was observed in Protocol B. Infarct size in control (n = 13) and treated (n = 13) groups was 44.2 +/- 2.6% versus 29.2 +/- 1.6%, respectively (p less than or equal to 0.005), with risk regions being 44.4 +/- 1.4% versus 46.0 +/- 1.6% (p = NS). Hemodynamic variables did not differ during the period of coronary artery occlusion. The respective collateral blood flows to the inner two thirds of the ischemic myocardium determined 60 minutes after occlusion were 0.05 +/- 0.01 ml/min/g and 0.06 +/- 0.04 ml/min/g (p = 0.806) for the PEG-ALB and PEG-SOD treated groups, respectively. Infarct size was related inversely to collateral blood flow in the PEG-ALB treated group. This relation shifted downward (analysis of covariance, p = 0.017). Plasma SOD activity in Protocols A sustained for 6 hours. Significant enzymatic activity was present after 4 days in Protocol B. Previous negative studies with native SOD may be related to the short half-life of its free-radical scavenging capacity, which compromises the chances of observing a protective effect after 4 days of reperfusion. The present results support our previous observations, as well as those of other investigators, demonstrating that superoxide dismutase can reduce that component of myocardial injury associated with reperfusion.
Durability of Response to Rilonacept (IL-1 Trap) in a Phase 3 Study of Patients with Cryopyrin-Associated Periodic Syndromes (CAPS): Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS)
Authors: H HOFFMAN, N AMAR, R CARTWRIGHT, A KIVITZ, P BELOMESTNOV, S MELLIS, S WEINSTEIN
Journal: Journal of Allergy and Clinical Immunology (2008)
The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor
Authors: J. A Bastarache, L. Wang, T. Geiser, Z. Wang, K. H Albertine, M. A Matthay, L. B Ware
Journal: Thorax (2007)

<b>Background:</b> The alveolar compartment is a procoagulant antifibrinolytic environment in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). A study was undertaken to test the hypothesis that the alveolar epithelium can initiate intra-alveolar coagulation by expressing active tissue factor (TF). <b>Methods:</b> Using an in vitro cell surface TF assay and TF ELISA, the activity and production of TF in cultured alveolar epithelial (A549) cells following exposure to cytomix (tumour necrosis factor α, interleukin 1β and interferon γ) was measured. TF gene transcription was measured by semi-quantitative reverse-transcription PCR. Immunohistochemistry for TF was performed on lung sections from patients with ARDS and controls. TF protein levels were measured by ELISA in undiluted pulmonary oedema fluid from patients with ALI/ARDS and compared with control patients with hydrostatic pulmonary oedema. <b>Results:</b> TF activity, mRNA and protein levels increased in A549 cells after stimulation with cytomix. Increased TF activity was also seen in A549 cells following incubation with pulmonary oedema fluid from patients with ALI/ARDS. Immunohistochemistry for TF in human lung tissue from patients with ARDS showed prominent TF staining in alveolar epithelial cells as well as intra-alveolar macrophages and hyaline membranes. TF antigen levels in oedema fluid (median 37 113 (IQR 14 956–73 525) pg/ml) were significantly higher than in plasma (median 336 (IQR 165–669) pg/ml, p&lt;0.001) in patients with ALI/ARDS, and TF procoagulant activity in oedema fluid was much higher than in plasma of these patients. Higher plasma levels were associated with mortality. <b>Conclusions:</b> The alveolar epithelium is capable of modulating intra-alveolar coagulation through upregulation of TF following exposure to inflammatory stimuli and may contribute to intra-alveolar fibrin deposition in ARDS.
Effectiveness of interventions to promote physical activity in children and adolescents: systematic review of controlled trials
Authors: Esther M F van Sluijs, Alison M McMinn, Simon J Griffin
Journal: BMJ (2007)

Objective To review the published literature on the effectiveness of interventions to promote physical activity in children and adolescents. Design Systematic review. Data sources Literature search using PubMed, SCOPUS, Psychlit, Ovid Medline, Sportdiscus, and Embase up to December 2006. Review methods Two independent reviewers assessed studies against the following inclusion criteria: controlled trial, comparison of intervention to promote physical activity with no intervention control condition, participants younger than 18 years, and reported statistical analyses of a physical activity outcome measure. Levels of evidence, accounting for methodological quality, were assessed for three types of intervention, five settings, and three target populations. Results The literature search identified 57 studies: 33 aimed at children and 24 at adolescents. Twenty four studies were of high methodological quality, including 13 studies in children. Interventions that were found to be effective achieved increases ranging from an additional 2.6 minutes of physical education related physical activity to 283 minutes per week of overall physical activity. Among children, limited evidence for an effect was found for interventions targeting children from low socioeconomic populations, and environmental interventions. Strong evidence was found that school based interventions with involvement of the family or community and multicomponent interventions can increase physical activity in adolescents. Conclusion Some evidence was found for potentially effective strategies to increase children's levels of physical activity. For adolescents, multicomponent interventions and interventions that included both school and family or community involvement have the potential to make important differences to levels of physical activity and should be promoted. A lack of high quality evaluations hampers conclusions concerning effectiveness, especially among children.
Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction
Authors: Elliott M. Antman, Hans W. Louwerenburg, Hubert F. Baars, Jan C.L. Wesdorp, Bas Hamer, Jean-Pierre Bassand, Frederique Bigonzi, Ghislaine Pisapia, C. Michael Gibson, Hein Heidbuchel, Eugene Braunwald, Frans Van de Werf
Journal: Circulation (2002)

Background — ENTIRE-TIMI 23 evaluated enoxaparin with full-dose tenecteplase (TNK) and half-dose TNK plus abciximab. Methods and Results — Patients (n=483) with ST-elevation MI presenting &lt;6 hours from symptom onset were randomized to full-dose TNK and either unfractionated heparin (UFH) (bolus 60 U/kg; infusion 12 U/kg per hour) or enoxaparin (1.0 mg/kg subcutaneously every 12 hours±initial 30 mg intravenous bolus), or half-dose TNK plus abciximab and either UFH (bolus 40 U/kg; infusion 7 U/kg per hour) or enoxaparin (0.3 to 0.75 mg/kg subcutaneously every 12 hours±initial intravenous bolus of 30 mg). With full-dose TNK and UFH, the rate of TIMI 3 flow at 60 minutes was 52% and was 48% to 51% with enoxaparin. Using combination therapy, the rate of TIMI 3 flow was 48% with UFH and 47% to 58% with enoxaparin. The rate of TIMI 3 flow among all UFH patients was 50% and was 51% among enoxaparin patients. Through 30 days, death/recurrent MI occurred in the full-dose TNK group in 15.9% of patients with UFH and 4.4% with enoxaparin ( P =0.005). In the combination therapy group, the rates were 6.5% with UFH and 5.5% with enoxaparin. The rate of major hemorrhage with full-dose TNK was 2.4% with UFH and 1.9% with enoxaparin; with combination therapy, it was 5.2% using UFH and 8.5% with enoxaparin. Conclusions — Enoxaparin is associated with similar TIMI 3 flow rates as UFH at an early time point while exhibiting advantages over UFH with respect to ischemic events through 30 days. These findings with enoxaparin are achieved with a similar risk of major hemorrhage.
Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis
Authors: S. R. Walmsley, A. S. Cowburn, M. R. Clatworthy, N. W. Morrell, E. C. Roper, V. Singleton, P. Maxwell, M. K. B. Whyte, E. R. Chilvers
Journal: Blood (2006)
Aurora A Regulates Prometaphase Progression by Inhibiting the Ability of RASSF1A to Suppress APC-Cdc20 Activity
Authors: Su Jung Song, Min Sup Song, Soon Jung Kim, So Yeon Kim, Seung Hae Kwon, Jhin Gook Kim, Diego F. Calvisi, Dongmin Kang, Dae-Sik Lim
Journal: Cancer Research (2009)

The Aurora (Ipl) kinase family plays important roles in the regulation of mitosis and tumorigenesis. The tumor suppressor RASSF1A controls mitotic progression by regulating anaphase-promoting complex (APC)-Cdc20 activity and microtubule stability, but the mechanism by which this action is regulated has not been previously established. Here, we show that Aurora A and B associate with and phosphorylate RASSF1A on serine 203 in vivo at different times and in different subcellular compartments during mitosis. Notably, both depletion of Aurora A by RNA interference and expression of a nonphosphorylatable RASSF1A (S203A) mutant gene led to a marked delay in prometaphase progression. This is likely because of the failure of RASSF1A to dissociate from Cdc20, constitutive inhibition of APC-Cdc20, and accumulation of mitotic cyclins. In contrast, the delay in prometaphase progression caused by Aurora A depletion was largely normalized by phosphomimetic RASSF1A (S203D). Finally, RASSF1A phosphorylation on serine 203 was up-regulated in Aurora A-overexpressing human tumors. These findings indicate that Aurora A plays a critical role in RASSF1A-APC-Cdc20 regulatory mechanisms that control normal prometaphase progression and that are involved in tumorigenesis. [Cancer Res 2009;69(6):2314-23.
Hu antigen R and tristetraprolin: Counter-regulators of rat apical sodium-dependent bile acid transporter by way of effects on messenger RNA stability
Authors: Frank Chen, Ann-Bin Shyu, Benjamin L. Shneider
Journal: Hepatology (2011)

The apical sodium-dependent bile acid transporter (ASBT, SLC10A2) mediates intestinal, renal, and cholangiocyte bile acid reclamation. Transcriptional regulation of ASBT is well described, whereas information on posttranscriptional regulation is limited. Prior studies suggested that ontogeny of ASBT is controlled in part by changes in messenger RNA (mRNA) stability. We studied the role that Hu antigen R (HuR) and tristetraprolin (TTP) play in regulating the expression of mRNA that contains the 3' untranslated region (UTR) of rat ASBT. The 3'UTR was incorporated into an SV-40 driven luciferase reporter (rASBT3-luciferase) for rapid screening of regulatory effects. Silencing HuR reduced luciferase reporter activity, whereas silencing TTP enhanced luciferase activity. Conversely, overexpression of HuR enhanced rASBT3-luciferase reporter activity. The same 3'UTR fragments of rat ASBT were incorporated into a beta-globin coding mRNA construct for analysis of mRNA stability (rASBT3-βglobin). mRNA half-life was progressively shortened by the incorporation of increasing sized fragments of the 3'UTR. Silencing HuR shortened the half-life of rASBT3-βglobin containing 0.3 kb of the rat ASBT 3'UTR. Gel shift assays revealed binding of HuR and TTP to rat ASBT 3'UTR. Endogenously expressed human ASBT mRNA half-lives and steady-state protein levels in Caco-2 cells were repressed when HuR was silenced but was enhanced when TTP was silenced. Developmental changes in HuR and TTP protein abundance correlated with previously characterized ontogenic changes in rat ileal and renal ASBT expression.These studies not only show that ASBT expression is controlled at the level of mRNA stability by way of its 3'UTR, but also identify HuR and TTP as two key transacting factors that are involved in exerting counterregulatory effects on ASBT mRNA stability.
Lingual Nerve Entrapment in Muscular and Osseous Structures
Authors: Maria Piagkou, Theano Demesticha, Giannoulis Piagkos, Androutsos Georgios, Skandalakis Panagiotis
Journal: International Journal of Oral Science (2010)

Running through the infratemporal fossa is the lingual nerve (i.e. the third branch of the posterior trunk of the mandibular nerve). Due to its location, there are various anatomic structures that might entrap and potentially compress the lingual nerve. These anatomical sites of entrapment are: (a) the partially or completely ossified pterygospinous or pterygoalar ligaments; (b) the large lamina of the lateral plate of the pterygoid process; and (c) the medial fibers of the anterior region of the lateral pterygoid muscle. Due to the connection between these nerve and anatomic structures, a contraction of the lateral pterygoid muscle, for example, might cause a compression of the lingual nerve. Any variations in the course of the lingual nerve can be of clinical significance to surgeons and neurologists because of the significant complications that might occur. To name a few of such complications, lingual nerve entrapment can lead to: (a) numbness, hypoesthesia or even anesthesia of the tongue's mucous glands; (b) anesthesia and loss of taste in the anterior two-thirds of the tongue; (c) anesthesia of the lingual gums; and (d) pain related to speech articulation disorder. Dentists should, therefore, be alert to possible signs of neurovascular compression in regions where the lingual nerve is distributed.
The Utility of MGPS in the Prognostic Factor of the Patients with Unresectable Colorectal Cancer
Authors: Y. Sakamoto, Y. Miyamoto, N. Ozaki, T. Ishimoto, M. Iwatsuki, S. Iwagami, Y. Baba, N. Yoshida, M. Watanabe, H. Baba
Journal: Annals of Oncology (2013)
Circulating antibodies to common food antigens in Japanese children with IDDM
Authors: Tahmeed Ahmed, Tomohiro Kamota, Ryo Sumazaki, Masanao Shibasaki, Takeki Hirano, Hitoshi Takita
Journal: Diabetes Care (1997)

OBJECTIVE To investigate the humoral immune response to common food antigens in Japanese children with IDDM. RESEARCH DESIGN AND METHODS IgG antibodies to cow's milk, β-lactoglobulin, bovine serum albumin (BSA), alpha-lactalbumin, and hen's egg ovalbumin were examined by enzyme-linked immunosorbent assay in the sera of 33 patients with IDDM, ages 11.8 ± 3.4 years. The data were compared with that of 50 normal subjects, ages 10.3 ± 5.1 years, who acted as control subjects. A positive antibody to a food antigen was defined as an antibody titer greater than the 95th percentile value in normal subjects. RESULTS Children with IDDM had significantly higher median titers of IgG antibodies to β-lactoglobulin and ovalbumin (P = 0.03 and P = 0.0005 respectively). More children with IDDM than control subjects had positive IgG antibody to ovalbumin (21 vs. 6%, P = 0.04). Titers, as well as the number of positive antibodies to other food antigens, including BSA, did not differ between the two groups. CONCLUSIONS Japanese children with IDDM show an enhanced humoral immune response to β-lactoglobulin and ovalbumin, a phenomenon that may be related to the pathogenesis of the disease.
Effects of Beta-Receptor Blockade on the Systemic and Coronary Hemodynamic Response to an Increasing Ventricular Rate in the Unanesthetized Dog
Authors: Fred R. Cobb, Robert J. Bache, Paul A. Ebert, Judith C. Rembert, Joseph C. Greenfield
Journal: Circulation Research (1969)

Phasic coronary and aortic blood flow and arterial pressure were measured as heart rates were increased by ventricular pacing from 120 to 270 beats/min in unanesthetized dogs before and after beta-receptor blockade with intravenous propranolol. Before beta-receptor blockade, coronary flow progressively increased and coronary vascular resistance decreased with increasing heart rates. Aortic blood flow and arterial pressure were not significantly altered at rates below 240 beats/min. After administration of propranolol, mean coronary blood flow was comparable to that before beta-receptor blockade at heart rates from 120 to 210 beats/min. However, aortic flow progressively decreased and peripheral resistance increased with increasing ventricular rates. At heart rates above 210 beats/min after propranolol coronary vascular resistance increased and coronary flow decreased. These data ascribe considerable importance to beta-receptor activity in the normal hemodynamic adjustments to rapid heart rates.
Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Preserved Ejection Fraction Is Associated With Higher Afterload and Reduced Survival
Authors: Zeineb Hachicha, Jean G. Dumesnil, Peter Bogaty, Philippe Pibarot
Journal: Circulation (2007)

Background— Recent studies and current clinical observations suggest that some patients with severe aortic stenosis on the basis of aortic valve area may paradoxically have a relatively low gradient despite the presence of a preserved left ventricular (LV) ejection fraction. The objective of the present study was to document the prevalence, potential mechanisms, and clinical relevance of this phenomenon. Methods and Results— We retrospectively studied the clinical and Doppler echocardiographic data of 512 consecutive patients with severe aortic stenosis (indexed aortic valve area ≤0.6 cm 2 · m −2 ) and preserved LV ejection fraction (≥50%). Of these patients, 331 (65%) had normal LV flow output defined as a stroke volume index &gt;35 mL · m 2 , and 181 (35%) had paradoxically low-flow output defined as stroke volume index ≤35 mL · m −2 . When compared with normal flow patients, low-flow patients had a higher prevalence of female gender ( P &lt;0.05), a lower transvalvular gradient (32±17 versus 40±15 mm Hg; P &lt;0.001), a lower LV diastolic volume index (52±12 versus 59±13 mL · m −2 ; P &lt;0.001), lower LV ejection fraction (62±8% versus 68±7%; P &lt;0.001), a higher level of LV global afterload reflected by a higher valvulo-arterial impedance (5.3±1.3 versus 4.1±0.7 mm Hg · mL −1 · m −2 ; P &lt;0.001) and a lower overall 3-year survival (76% versus 86%; P =0.006). Only age (hazard ratio, 1.04; 95% CI, 1.01 to 1.08; P =0.025), valvulo-arterial impedance &gt;5.5 mm Hg · mL −1 · m −2 (hazard ratio, 2.6; 95% CI, 1.2 to 5.7; P =0.017), and medical treatment (hazard ratio, 3.3; 95% CI, 1.8 to 6.7; P =0.0003) were independently associated with increased mortality. Conclusion— Patients with severe aortic stenosis may have low transvalvular flow and low gradients despite normal LV ejection fraction. A comprehensive evaluation shows that this pattern is in fact consistent with a more advanced stage of the disease and has a poorer prognosis. Such findings are clinically relevant because this condition may often be misdiagnosed, which leads to a neglect and/or an underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery.
Treatment of bites by adders and exotic venomous snakes
Authors: David A Warrell
Journal: BMJ (2005)

<b>Objectives</b> To assess the clinical effectiveness, effect on waiting times, and patient acceptability of PhysioDirect services in patients with musculoskeletal problems, compared with usual care. <b>Design</b> Pragmatic randomised controlled trial to assess equivalence in clinical effectiveness. Patients were individually randomised in a 2:1 ratio to PhysioDirect or usual care. <b>Setting</b> Four physiotherapy services in England. <b>Participants</b> Adults (aged ≥18 years) referred by general practitioners or self referred for musculoskeletal physiotherapy. <b>Interventions</b> PhysioDirect services invited patients to telephone a physiotherapist for initial assessment and advice, followed by face-to-face physiotherapy if necessary. Usual care involved patients joining a waiting list for face-to-face treatment. <b>Main outcome measures</b> Numbers of appointments, waiting time for treatment, and non-attendance rates. Primary outcome was physical health (SF-36v2 physical component score) at six months. Secondary outcomes included four other measures of health outcome, mental component score and scales from the SF-36v2, time lost from work, and patient satisfaction and preference. Participants were not blind to allocation, but outcome data were collected blind to allocation. <b>Results</b> Of 1506 patients allocated to PhysioDirect and 743 to usual care, 85% provided primary outcome data at six months (1283 and 629 patients, respectively). PhysioDirect patients had fewer face-to-face appointments than usual care patients (mean 1.91 <i>v</i> 3.11; incidence rate ratio 0.59 (95% confidence interval 0.53 to 0.65)), a shorter waiting time (median 7 days <i>v</i> 34 days; arm time ratio 0.32 (0.29 to 0.35)), and lower rates of non-attendance (incidence rate ratio 0.55 (0.41 to 0.73)). After six months' follow-up, the SF-36v2 physical component score was equivalent between groups (adjusted difference in means −0.01 (−0.80 to 0.79)). Health outcome measures suggested a trend towards slightly greater improvement in the PhysioDirect arm at six week follow-up and no difference at six months. There was no difference in time lost from work. PhysioDirect patients were no more satisfied with access to physiotherapy than usual care patients, but had slightly lower satisfaction overall at six months (difference in satisfaction −3.8% (−7.3% to −0.3%); P=0.031). PhysioDirect patients were more likely than usual care patients to prefer PhysioDirect in future. No adverse events were detected. <b>Conclusions</b> PhysioDirect is equally clinically effective compared with usual care, provides faster access to physiotherapy, and seems to be safe. However, it could be associated with slightly lower patient satisfaction. <b>Trial registration</b> Current Controlled Trials ISRCTN55666618.
Concrete magnitudes: From numbers to time
Authors: Christine M. Falter, Valdas Noreika, Julian Kiverstein, Bruno Mölder
Journal: Behavioral and Brain Sciences (2009)

Abstract Cohen Kadosh &amp; Walsh (CK&amp;W) present convincing evidence indicating the existence of notation-specific numerical representations in parietal cortex. We suggest that the same conclusions can be drawn for a particular type of numerical representation: the representation of time. Notation-dependent representations need not be limited to number but may also be extended to other magnitude-related contents processed in parietal cortex (Walsh 2003).