tbuckley/cabot-search huggingface dataset:
On the use of mobile inflatable hypoxic marquees for sport-specific altitude training in team sports
Authors: Olivier Girard, Franck Brocherie, Grégoire P Millet
Journal: British Journal of Sports Medicine (2013)

Background/aim With the evolving boundaries of sports science and greater understanding of the driving factors in the human performance physiology, one of the limiting factors has now become the technology. The growing scientific interest on the practical application of hypoxic training for intermittent activities such as team and racket sports legitimises the development of innovative technologies serving athletes in a sport-specific setting. Methods Description of a new mobile inflatable simulated hypoxic equipment. Results The system comprises two inflatable units—that is, a tunnel and a rectangular design, each with a 215 m 3 volume and a hypoxic trailer generating over 3000 Lpm of hypoxic air with FiO 2 between 0.21 and 0.10 (a simulated altitude up to 5100 m). The inflatable units offer a 45 m running lane (width=1.8 m and height=2.5 m) as well as a 8 m×10 m dome tent. FiO 2 is stable within a range of 0.1% in normal conditions inside the tunnel. The air supplied is very dry—typically 10–15% relative humidity. Conclusions This mobile inflatable simulated hypoxic equipment is a promising technological advance within sport sciences. It offers an opportunity for team-sport players to train under hypoxic conditions, both for repeating sprints (tunnel configuration) or small-side games (rectangular configuration).
Dynamics of Reductive Genome Evolution in Mitochondria and Obligate Intracellular Microbes
Authors: Amit N. Khachane, Kenneth N. Timmis, Vítor A. P. Martins dos Santos
Journal: Molecular Biology and Evolution (2006)

Reductive evolution in mitochondria and obligate intracellular microbes has led to a significant reduction in their genome size and guanine plus cytosine content (GC). We show that genome shrinkage during reductive evolution in prokaryotes follows an exponential decay pattern and provide a method to predict the extent of this decay on an evolutionary timescale. We validated predictions by comparison with estimated extents of genome reduction known to have occurred in mitochondria and Buchnera aphidicola, through comparative genomics and by drawing on available fossil evidences. The model shows how the mitochondrial ancestor would have quickly shed most of its genome, shortly after its incorporation into the protoeukaryotic cell and prior to codivergence subsequent to the split of eukaryotic lineages. It also predicts that the primary rickettsial parasitic event would have occurred between 180 and 425 million years ago (MYA), an event of relatively recent evolutionary origin considering the fact that Rickettsia and mitochondria evolved from a common alphaproteobacterial ancestor. This suggests that the symbiotic events of Rickettsia and mitochondria originated at different time points. Moreover, our model results predict that the ancestor of Wigglesworthia glossinidia brevipalpis, dated around the time of origin of its symbiotic association with the tsetse fly (50–100 MYA), was likely to have been an endosymbiont itself, thus supporting an earlier proposition that Wigglesworthia, which is currently a maternally inherited primary endosymbiont, evolved from a secondary endosymbiont.
Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry.
Authors: S P Stabler, P D Marcell, E R Podell, R H Allen, D G Savage, J Lindenbaum
Journal: Journal of Clinical Investigation (1988)

To determine if levels of serum total homocysteine are elevated in patients with either cobalamin or folate deficiency, we utilized a new capillary gas chromatographic-mass spectrometric technique to measure total homocysteine in the serum of 78 patients with clinically confirmed cobalamin deficiency and 19 patients with clinically confirmed folate deficiency. Values ranged from 11 to 476 mumol/liter in the cobalamin-deficient patients and 77 of the 78 patients had values above the normal range of 7-22 mumol/liter as determined for 50 normal blood donors. In the cobalamin-deficient patients, serum total homocysteine was positively correlated with serum folate, mean corpuscular volume, serum lactate dehydrogenase, serum methylmalonic acid, and the degree of neurologic involvement, and inversely correlated with platelets and hematocrit. In the folate-deficient patients, values for serum total homocysteine ranged from 17 to 185 mumol/liter and 18 of the 19 patients had values above the normal range. Some patients with pernicious anemia who were intermittently treated with cyanocobalamin were found to have elevated serum levels of total homocysteine while they were free of hematologic and neurologic abnormalities. The measurement of serum total homocysteine will help define the incidence of cobalamin deficiency and folate deficiency in various patient populations.
Comparing Signaling Networks between Normal and Transformed Hepatocytes Using Discrete Logical Models
Authors: Julio Saez-Rodriguez, Leonidas G. Alexopoulos, MingSheng Zhang, Melody K. Morris, Douglas A. Lauffenburger, Peter K. Sorger
Journal: Cancer Research (2011)

Abstract Substantial effort in recent years has been devoted to constructing and analyzing large-scale gene and protein networks on the basis of “omic” data and literature mining. These interaction graphs provide valuable insight into the topologies of complex biological networks but are rarely context specific and cannot be used to predict the responses of cell signaling proteins to specific ligands or drugs. Conversely, traditional approaches to analyzing cell signaling are narrow in scope and cannot easily make use of network-level data. Here, we combine network analysis and functional experimentation by using a hybrid approach in which graphs are converted into simple mathematical models that can be trained against biochemical data. Specifically, we created Boolean logic models of immediate-early signaling in liver cells by training a literature-based prior knowledge network against biochemical data obtained from primary human hepatocytes and 4 hepatocellular carcinoma cell lines exposed to combinations of cytokines and small-molecule kinase inhibitors. Distinct families of models were recovered for each cell type, and these families clustered topologically into normal and diseased sets. Cancer Res; 71(16); 5400–11. ©2011 AACR.
Cardiac adenoviral S100A1 gene delivery rescues failing myocardium
Authors: Patrick Most, Sven T. Pleger, Mirko Völkers, Beatrix Heidt, Melanie Boerries, Dieter Weichenhan, Eva Löffler, Paul M.L. Janssen, Andrea D. Eckhart, Jeffrey Martini, Matthew L. Williams, Hugo A. Katus, Andrew Remppis, Walter J. Koch
Journal: Journal of Clinical Investigation (2004)

Cardiac-restricted overexpression of the Ca2+-binding protein S100A1 has been shown to lead to increased myocardial contractile performance in vitro and in vivo. Since decreased cardiac expression of S100A1 is a characteristic of heart failure, we tested the hypothesis that S100A1 gene transfer could restore contractile function of failing myocardium. Adenoviral S100A1 gene delivery normalized S100A1 protein expression in a postinfarction rat heart failure model and reversed contractile dysfunction of failing myocardium in vivo and in vitro. S100A1 gene transfer to failing cardiomyocytes restored diminished intracellular Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ load mechanistically due to increased SR Ca2+ uptake and reduced SR Ca2+ leak. Moreover, S100A1 gene transfer decreased elevated intracellular Na+ concentrations to levels detected in nonfailing cardiomyocytes, reversed reactivated fetal gene expression, and restored energy supply in failing cardiomyocytes. Intracoronary adenovirus-mediated S100A1 gene delivery in vivo to the postinfarcted failing rat heart normalized myocardial contractile function and Ca2+ handling, which provided support in a physiological context for results found in myocytes. Thus, the present study demonstrates that restoration of S100A1 protein levels in failing myocardium by gene transfer may be a novel therapeutic strategy for the treatment of heart failure.
Pertussis toxin-treated dog: a whole animal model of impaired inhibitory regulation of adenylate cyclase.
Authors: J W Fleming, T D Hodges, A M Watanabe
Journal: Circulation Research (1988)

We have shown previously that stimulation of high-affinity GTP hydrolysis and inhibition of adenylate cyclase activity by muscarinic agonists are mediated by pertussis toxin (IAP) substrates (Gi and Go) in canine cardiac sarcolemma. We have now used the pertussis toxin-treated dog as a whole animal model in which Gi- and Go-mediated biochemical mechanisms can be studied. Mongrel dogs were injected intravenously with IAP 48 hours prior to death and isolation of left ventricular sarcolemma. Treatment of the animal in vivo with the toxin prevented subsequent in vitro IAP-catalyzed [32P]ADP-ribosylation of substrates in cardiac, erythrocytic, and renal cortical plasma membranes, suggesting that ADP-ribosylation occurred in vivo from endogenous substrate. Consistent with our previous results obtained by treating sarcolemma in vitro with IAP, muscarinic receptor-mediated stimulation of high-affinity GTP hydrolysis and inhibition of GTP-activated adenylate cyclase activity were attenuated in sarcolemma purified from the toxin-treated animals. Proximal to adenylate cyclase, guanine nucleotide regulation of muscarinic receptor affinity for agonists was also abolished in membranes from the toxin-treated animals. In addition, the ability of oxotremorine to attenuate GTP regulation of stimulation of adenylate cyclase activity by magnesium ions was abolished in sarcolemma from the IAP-treated dogs. Thus, cardiac sarcolemma isolated from the IAP-treated animals displayed biochemical characteristics of an adenylate cyclase system in which inhibitory regulatory pathways had been attenuated. The cardiac biochemical studies and the in vivo ADP-ribosylation of noncardiac IAP substrates also suggests considerable potential use of this model in the physiological and biochemical study of regulatory mechanisms mediated by GTP-binding proteins in other systems.
Reduction in plasma or Skin Alpha Tocopherol Concentration With Long-term Oral Administration of Beta-carottene in Humans and Mice
Authors: M. J. Xu, P. M. Plezia, D. S. Alberts, S. S. Emerson, Y. M. Peng, S. M. Sayers, Y. Liu, C. Ritenbaugh, H. L. Gensler
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal Studies, in cluding our own, have documented that dietary betacarotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical of pharmacokinetic ramifications of long-term, high-dose beta -carotene regimens on other fat-soluble vitamines sugh as alpha-tocopherol. purpose : This study was designed to determine on plasma concentrations of alphatocopherol in normal human subjects and in an experimental C3H/HeH mouse model, Methods ; In a doubleblind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 310, 45, or 60 mg of oral betacarotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-fie C3H/HeH mice were fed a basal diet with of without beta-carotene and treated topically with or without alpha-tocopherolo, except for the control mice, which received UV radiation for 27 weeks from week 3 to week 30. plasma and dorsal skin samples were taken after 40 weeks and were analyzed for alpha-tocopherol and /or beta-carotene by highperformance liquid chromatography. Results : Long-term dietary beta-carotene administration resulted in statistically significant reductions in levels of alpha-tocopherol in the skin and plasma of UV-irradiated mice. In the human study, the decrease in plasma alpha-tocopherol levels was progressive and significant between 6 and 9 months of beta-carotene dosing in all dosage groups. The greatest decrease was observed during the 9th (last) moths of dosing with a secrease of 40& from baseline. All oral betacarotene doses (15–60 mg/d, hoowever, resultedin similar and in only small differenses in beta-carotene plasma levels. Conclusion : Long-term oral adminiatration of beta carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-responce effect between dose of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the for beta-carotene dose groups. Implications : Studies are needed to determine how long-term beta-carotne dosing influences tissue distribution of dietary alphatopherol. Careful surveillance for this ad other potentially harmful nutrient interactions should become part of all long-term intervention studies.[J Natl Cancer Inst 84: 1559–1565, 1992]
Systemic literature review of the performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis: good news of debatable significance
Authors: H Zeidler
Journal: Annals of the Rheumatic Diseases (2013)

Radner et al 1report the results of a systematic literature search analysing the numerous articles and conference proceedings which have examined the performance of the 2010 ACR/EULAR classification criteria for rheumatoid arthritis (RA). Their comprehensive evaluation determined whether the 2010 criteria were applied correctly in accordance with the original publication, explored the performance of the criteria as regards different methods for assessing the criteria components and using different reference standards, and finally, directly compared classification results obtained using the 2010 or the 1987 criteria. The overall sensitivity of the criteria was 82% and overall specificity was 61% when applied to the intended target population. Eight studies and five meeting abstracts directly compared the 1987 and 2010 criteria using different reference standards within different target populations. When patients with other diagnoses were excluded, the 2010 ACR/EULAR criteria demonstrated almost 21% higher sensitivity compared with the 1987 ACR criteria, although specificity was 16% lower. Therefore, Radner et al 1 conclude that the 2010 criteria are more sensitive than the 1987 criteria at the cost of a slight decrement in specificity, which might increase the possibility that a few non-RA patients are classified as RA patients and, for example, entered into clinical trials. Another recent systematic literature review and meta-analysis including six full papers and four abstracts reported an identical result, stating that the new classification criteria have good sensitivity, lower specificity and an overall moderate …
Mood Improvement Following Daily Left Prefrontal Repetitive Transcranial Magnetic Stimulation in Patients With Depression: A Placebo-Controlled Crossover Trial
Authors: Mark S. George, Eric M. Wassermann, Tim A. Kimbrell, John T. Little, Wendol E. Williams, Aimee L. Danielson, Benjamin D. Greenberg, Mark Hallett, Robert M. Post
Journal: American Journal of Psychiatry (1997)

Preliminary studies have indicated that daily left prefrontal repetitive transcranial magnetic stimulation might have antidepressant activity. The authors sought to confirm this finding by using a double-blind crossover design.Twelve depressed adults received in random order 2 weeks of active treatment (repetitive transcranial magnetic stimulation, 20 Hz at 80% motor threshold) and 2 weeks of sham treatment.Changes from the relevant phase baseline in scores on the 21-item Hamilton depression scale showed that repetitive transcranial magnetic stimulation significantly improved mood over sham treatment. During the active-treatment phase, Hamilton depression scale scores decreased 5 points, while during sham treatment the scores increased or worsened by 3 points. No adverse effects were noted.These placebo-controlled results suggest that daily left prefrontal repetitive transcranial magnetic stimulation has antidepressant activity when administered at these parameters. Further controlled studies are indicated to explore optimal stimulation characteristics and location, potential clinical applications, and possible mechanisms of action.
Measurement of inflammatory indices in induced sputum: effects of selection of sputum to minimize salivary contamination
Authors: E Pizzichini, MM Pizzichini, A Efthimiadis, FE Hargreave, J Dolovich
Journal: European Respiratory Journal (1996)

Sputum examination is being used increasingly as a noninvasive method to assess airway inflammation. Expectorated sputum has variable contamination with saliva. Methods of processing have included the selection of portions of the sample considered to be representative of pulmonary origin versus use of the whole specimen, which is confounded by varying volumes of saliva. We compared cell profiles and eosinophilic cationic protein (ECP) concentration in sputum selected from the expectorate and in the usually discarded residual portion to determine to what degree salivary contamination is minimized and if the results are representative of lower respiratory secretions. Sputum was induced with hypertonic saline in six healthy and nine asthmatic subjects. All portions considered to be of pure lower respiratory tract origin were selected from the residual. The selected and residual portions were treated with dithiothreitol, total cell counts and cell viability were obtained, cytospins were made for differential cell counts and supernatant was collected for ECP assay. Selected portions of the specimens, in comparison with the residual portion showed: little squamous cell contamination (median 1.2 vs 70%; p &lt; 0.001); higher total cell counts.mL-1 (5.1 vs 0.5 x 10(6) cells.mL-1; p &lt; 0.001); higher number of viable nonsquamous cells per sample (1.9 vs 0.6 x 10(6) cells; p &lt; 0.001); higher slide quality score (7 vs 4; p &lt; 0.001); and higher levels of ECP (768 vs 136 micrograms.L-1; p &lt; 0.001). There were no differences in the differential cell counts of eosinophils (1.3 vs 3.8%), neutrophils (44 vs 32%), and lymphocytes (0.6 vs 0.6%). While the proportion of macrophages was lower (36 vs 54%; p &lt; 0.05), the absolute number (41 vs 19 x 10(4) cells; p &lt; 0.05) was higher in the selected portion. In summary, selection of all portions of induced sputum from the expectorate minimized the confounding influence of saliva. Loss of nonsquamous cells in the residual portion was variable but usually less than one third of those in the selected portion. With one exception, this loss had little influence on the differential counts of inflammatory cells. Similar observations apply to eosinophilic cationic protein levels. We conclude that, in healthy subjects and treated asthmatics, inflammatory markers in the selected portion of the expectorate can be used to represent those in the lower respiratory tract in general.
The perfect storm: challenges and opportunities for translational medicine
Authors: William C. Hahn
Journal: Journal of Clinical Investigation (2013)

It truly has been an honor and a privilege to have served as the President of the ASCI for the last year, and as has been the tradition since the founding of the Society in 1909, I stand here with more than a little trepidation to deliver an address where the expectation is that I will have something profound, witty, and maybe even important to say. Indeed, although my tenure as the President of the ASCI has been entirely enjoyable, I have lived under the terrible knowledge that I would be standing here today giving this address.
Pancreatic epithelial fluid and bicarbonate secretion is significantly elevated in the absence of peripheral serotonin
Authors: József Maléth, Tamara Madácsy, Petra Pallagi, Anita Balázs, Viktória Venglovecz, Zoltán Rakonczay, Péter Hegyi
Journal: Gut (2015)

We read the manuscript by Sonda et al 1 recently published in Gut with great interest. The authors elegantly demonstrated that lack of peripheral serotonin (5-HT) in tryptophan hydroxylase 1 knockout (TPH1−/−) mice remarkably limited pancreatic damage and leucocyte infiltration during the early phase of cerulein-induced acute pancreatitis (AP) and identified 5-HT as an important regulator of zymogen secretion in acinar cells. Although the study was very comprehensive, the ductal function of TPH1−/− mice was not investigated, which might be another key player in this protection. Notably, 5-HT was shown to inhibit fluid and HCO3− secretion of pancreatic ductal epithelial cells,2 which play a pivotal role in pancreatic physiology and can influence the severity of AP.3 Thus, we investigated the possible alterations of pancreatic ductal secretion in TPH1−/− mice.

To achieve our aim, intralobular/interlobular pancreatic ducts were isolated from the pancreas of wild-type (TPH1+/+) and TPH1−/− mice. HCO3− secretion was measured by three different, but complementary methods using …
The Inflammasome in Atherosclerosis and Type 2 Diabetes
Authors: Seth L. Masters, Eicke Latz, Luke A. J. O’Neill
Journal: Science Translational Medicine (2011)

Atherosclerosis is the cause of morbiditiy for 70% of patients with type 2 diabetes. In both of these diseases, a protein complex known as the inflammasome is stimulated to activate interleukin-1β (IL-1β) and IL-18, which are pathogenic inflammatory cytokines. Triggers for the inflammasome are obesity-related factors, such as cholesterol crystals in atherosclerosis, or hyperglycemia, ceramides, and islet amyloid polypeptide in type 2 diabetes. Therapeutics that target IL-1β in clinical trials for type 2 diabetes might also decrease the incidence of atherosclerosis.
Breast Implants and Connective-Tissue Disease
Authors: S. Elizabeth Whitmore
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The article by Dr Hennekens and colleagues<sup>1</sup>lends further support to recent epidemiologic studies finding that breast implants are associated with no or only a small increased risk of connective-tissue diseases<sup>2</sup>and breast cancer.<sup>3</sup>Despite these studies, the public is being led to believe that implants are associated with or cause various diseases, as has been implied by the Dow Corning class action suit and more than a dozen articles in popular women's magazines.<sup>4</sup>For many reasons, including the divergence of medical and public perceptions and the potential for loss of precious public trust, the medical field should closely scrutinize these studies for errors in design and analysis that result in missed associations. One possible error is inattention to a potential confounder, estrogen serum level and tissue sensitivity. Estrogen is important in the pathogenesis of breast cancer, may play a predisposing role in connective-tissue diseases, and
Rectal potential difference in the diagnosis of aldosterone excess.
Authors: D G Beevers, J J Morton, M Tree, J Young
Journal: Gut (1975)

Rectal potential difference (pd) is directly related to the plasma aldosterone concentration, and rises when aldosterone is stimulated by sodium deprivation. However, when the measurement of rectal pd was tested at a screening test for hyperaldosteronism in 19 hypertensive subjects, four of the eight with primary hyperaldosteronism had a normal pd and four of the eight without aldosterone excess had an abnormally raised potential difference. The technique cannot therefore be recommended as a routine screening test for hyperaldosteronism. No relationship was found between rectal pd and hypertension associated with excess of deoxycorticosterone. Rectal pd rises in response to the mineralocorticoid-like agent carbenoxolone.