tbuckley/cabot-search huggingface dataset:
Warm-up exercise can reduce exercise-induced bronchoconstriction
Authors: Mark R Elkins, John D Brannan
Journal: British Journal of Sports Medicine (2012)

▸  Stickland MK , Rowe BH, et al. Medicine & Science in Sports & Exercise 2012; 44 (3):383–91.

Exercise-induced bronchoconstriction (EIB) is a transient narrowing of the lower airways after vigorous exercise.1 Exercise requires increased ventilation, which results in respiratory water loss leading to airway drying and cooling. Evaporative water loss leading to an increase in the osmolarity of the airway surface liquid and consequent release of mediators is thought to be the major stimulus and mechanism for EIB.2 Mast cell mediators include histamine, leukotrienes and prostaglandins, which act on specific receptors on the bronchial smooth muscle causing bronchoconstriction.3 Leukotrienes from eosinophils and neuropeptides from sensory nerves may also be involved in EIB. EIB can occur in people with or without chronic asthma, although it is highly prevalent in people with asthma.1

The intensity and duration of exercise are key determinants of the airway response.2 Guidelines therefore recommend an exercise challenge of 6–8 min at 80–90% of the predicted maximum heart rate.4 However, laboratory exercise may have poor sensitivity to identify EIB if the intensity does not induce enough ventilation to achieve an adequate rate of respiratory water loss. In athletes, field exercise, eucapnic hyperventilation or osmotic challenge may be more appropriate tests.3

A decrease in the forced expiratory volume in 1 s (FEV1) of 10–15% after exercise is the threshold for the diagnosis of EIB.4 ,5 EIB may be associated with cough, wheeze, chest pain or tightness, dyspnoea or excessive mucus production.6 However, the amount of bronchoconstriction does not always correlate well with the baseline level of lung function or presence or severity of symptoms.7 ,8 Nevertheless, these symptoms or the effect of bronchoconstriction on ventilation could limit athletic performance.

An initial airway response to exercise inducing a …
Quantitative Optical Spectroscopy: A Robust Tool for Direct Measurement of Breast Cancer Vascular Oxygenation and Total Hemoglobin Content <i>In vivo</i>
Authors: J. Quincy Brown, Lee G. Wilke, Joseph Geradts, Stephanie A. Kennedy, Gregory M. Palmer, Nirmala Ramanujam
Journal: Cancer Research (2009)

Abstract We propose the use of a robust, biopsy needle–based, fiber-optic tool for routine clinical quantification of tumor oxygenation at the time of diagnostic biopsy for breast cancer. The purpose of this study was to show diffuse reflectance spectroscopy as a quantitative tool to measure oxygenation levels in the vascular compartment of breast cancers in vivo via an optical biopsy technique. Thirty-five patients undergoing surgical treatment for breast cancer were recruited for the study at Duke University Medical Center. Diffuse reflectance spectroscopy was performed on the tumors in situ before surgical resection, followed by needle-core biopsy of the optically measured tissue. Hemoglobin saturation and total hemoglobin content were quantified from 76 optical spectra-tissue biopsy pairs, consisting of 20 malignant, 23 benign, and 33 adipose tissues. Hemoglobin saturation in malignant tissues was significantly lower than nonmalignant tissues (P &amp;lt; 0.002) and was negatively correlated with tumor size and pathologic tumor category (P &amp;lt; 0.05). Hemoglobin saturation was positively correlated with total hemoglobin content in malignant tissues (P &amp;lt; 0.02). HER2/neu-amplified tumors exhibited significantly higher total hemoglobin content (P &amp;lt; 0.05) and significantly higher hemoglobin saturation (P &amp;lt; 0.02), which is consistent with a model of increased angiogenesis and tumor perfusion promoted by HER2/neu amplification. Diffuse reflectance spectroscopy could aid in prognosis and prediction in breast cancer via quantitative assessment of tumor physiology at the time of diagnostic biopsy. [Cancer Res 2009;69(7):2919–26]
Phase II Study of a Liposome-Entrapped Cisplatin Analog (L-NDDP) Administered Intrapleurally and Pathologic Response Rates in Patients With Malignant Pleural Mesothelioma
Authors: Charles Lu, Roman Perez-Soler, Bilal Piperdi, Garrett L. Walsh, Stephen G. Swisher, W. Roy Smythe, Hyung J. Shin, Jae Y. Ro, Lei Feng, Mylene Truong, Adiseshu Yalamanchili, Gabriel Lopez-Berestein, Waun K. Hong, Abdul R. Khokhar, Dong M. Shin
Journal: Journal of Clinical Oncology (2005)

To determine pathologic response rates to liposome-entrapped cis-bisneodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (L-NDDP) administered intrapleurally in patients with malignant pleural mesothelioma.Thirty-three patients with malignant pleural mesothelioma and free-flowing pleural effusions received intrapleural L-NDDP once every 3 weeks at a dose of 450 mg/m2. Thoracoscopic evaluation with pleural biopsies was performed before therapy and then after every two cycles. The primary end point was pathologic response as determined by thoracoscopic biopsy.After at least two cycles, post-treatment pleural biopsy analysis was negative in 14 patients for a pathologic response rate of 42% (95% CI, 25% to 61%). Median survival was 11.2 months. There were three treatment-related deaths secondary to peritonitis, cellulitis at the thoracoscopy site, and empyema. Grade 3 nonhematologic toxicities included infection, fever, dyspnea, and anorexia, which occurred in five (15%), one (3%), one (3%), and one (3%) patients, respectively. There were no grade 4 nonhematologic toxicities. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in five (15%), three (9%), and two (6%) patients, respectively. Two patients with pathologic responses subsequently underwent pleural decortication. Both surgical specimens revealed residual tumor in regions that were not in direct communication with the pleural space.Intrapleural L-NDDP therapy in this patient population is feasible with significant but manageable toxicity. Although pathologic responses are highly encouraging, areas of mesothelioma that are not in direct communication with the pleural space will evade drug exposure and limit efficacy in some patients. The optimal role of intrapleural L-NDDP therapy currently remains to be determined.
W H R Rivers: portrait of a great physician in Pat Barker's Regeneration trilogy
Authors: Katherine G Nickerson, Steven Shea
Journal: The Lancet (1997)

1The term shell shock was first used during World War I to describe the physical and mental breakdown of men in the incomparable brutality of trench warfare; standard therapies for their nightmares, sleeplessness, panic attacks, mutism, paralysis, and other symptoms, included electric shocks to affected body parts, hypnosis, and electroconvulsive therapy. 2 Rivers took a more psychological approach, and his insights form the basis for a wider understanding of what we now call posttraumatic stress disorders. Well-versed in Freudian theory, Rivers maintained that war neuroses did not result from the war experiences themselves but were “due to the attempt to banish from the mind distressing memories”. 1 He attributed his own clinical successes mainly to encouraging patients to remember, but he also described more subtle aspects of therapy, which he termed “re-education” and “faith and suggestion”, by which he meant the role of the therapist in reframing painful memories and the power of the therapeutic relationship itself. The Lancet article is one of Pat Barker’s sources for her own three-volume meta-novel about Rivers: Regeneration, 3
Cell surface receptors and ectoenzymes in mesangial cells.
Authors: R Ardaillou, D Chansel, V Stefanovic, N Ardaillou
Journal: Journal of the American Society of Nephrology (1992)

Mesangial cells possess a variety of receptors for hormones and autacoids. They are also equipped with ectoenzymes whose function may be to control the availability of autacoids and hormones at their receptor sites. Several examples are considered. Receptors for angiotensin II (AII) are present both on murine and human mesangial cells. One single group of receptors has been demonstrated in each of these preparations. Mesangial cell AII receptors are linked to phospholipase C via a G protein. They belong to the AT1 subtype because (125I)AII is displaced from its binding sites preferentially by AT1 antagonists such as DUP 753 and EXP 3,174, whereas AT2 antagonists are much less potent. AT1 antagonists suppress the biological effects of AII in mesangial cells, including the stimulation of intracellular calcium concentration and the increase of prostaglandin synthesis and of (3H)leucine incorporation. Mesangial cells also have receptors for atrial natriuretic factor, but the distribution between B receptors with guanylate cyclase activity and clearance (C) receptors varies with the species. Both types are present in murine mesangial cells, whereas only C receptors are found in human mesangial cells. In contrast, human epithelial cells possess both B and C receptors. Ecto-5'-nucleotidase activity results in the production of adenosine, which acts on mesangial cells through A1 and A2 receptors. This enzyme is markedly induced in rat mesangial cells by interleukin-1, whose effect is mediated in part by prostaglandin E2 and cAMP. Various other cAMP-stimulating agents also induce 5'-nucleotidase expression in rat mesangial cells. Ectopeptidases are present in all glomerular cell types but essentially in epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial
Authors: Roger D James, Robert Glynne-Jones, Helen M Meadows, David Cunningham, Arthur Sun Myint, Mark P Saunders, Timothy Maughan, Alec McDonald, Sharadah Essapen, Martin Leslie, Stephen Falk, Charles Wilson, Simon Gollins, Rubina Begum, Jonathan Ledermann, Latha Kadalayil, David Sebag-Montefiore
Journal: The Lancet Oncology (2013)
Trichlorethylene as an Inhalation Anaesthetic
Authors: C. L. Hewer, C. F. Hadfield
Journal: BMJ (1941)

TUBERCULOSIS IN RECRUITS T}iEBRWTisrI-~~~~~~~~~~~~~~NEIA tion, and we are of opinion that our figures are significant enough to justify the adoption of a similar scheme in this country.Conclusions Of 1,869 recruits referred to the Welsh National Memorial Association's tuberculosis officers by the medical boards and then seen for the first time, 112 (6%) were founid to be suffering from active tuberculosis, as compared with 23.8% of imale neew cases in the same age group examined in 1940 in the ordinary course of work, and with 1.4% of the men called up and examined as a routine measure, and not because they were referred by medical boards, by Dr. Robert E. Plunkett.Of the 112 recruits found tuberculous, 108 (or 5.7% of all those referred) had pulmonary tuberculosis, and 4 (0.3%) non-pulmoniary tuberculosis.An additional 30 cases (1.6%) required further observa- tion.The percentage figures of cases found tuberculous analysed under the four main headings set out in Table II show that the indications for the reference of cases by medical boards to tuberculosis officers should be compre- hensive, and even then cases of active or latent tuberculosis may be missed.It is better that the total cases referred should be large, and the percentage found tuberculous low, than that only a few cases should be referred, with a high percentage found tuberculous.
Cost-Effectiveness of Coronary Artery Bypass Grafts Versus Percutaneous Coronary Intervention for Revascularization of High-Risk Patients
Authors: Kevin T. Stroupe, Douglass A. Morrison, Mark A. Hlatky, Paul G. Barnett, Lishan Cao, Christopher Lyttle, Denise M. Hynes, William G. Henderson
Journal: Circulation (2006)

A Department of Veterans Affairs Cooperative Study randomized high-risk patients with medically refractory myocardial ischemia, a group largely excluded from previous trials, to urgent revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The present study examined the cost-effectiveness of PCI versus CABG for these high-risk patients.Of 454 patients at 16 Department of Veterans Affairs medical centers, 445 were available for the economic analysis (218 PCI and 227 CABG patients). Total costs were assessed at 3 and 5 years from the third-party payer's perspective, and effectiveness was measured by survival. After 3 years, average total costs were 63,896 dollars for PCI versus 84,364 dollars for CABG patients, a difference of 20,468 dollars (95% confidence interval [CI] 13,918 dollars to 27,569 dollars). CIs were estimated by bootstrapping. Survival at 3 years was 0.82 for PCI versus 0.79 for CABG patients (P=0.34). Precision of the cost-effectiveness estimates were assessed by bootstrapping. PCI was less costly and more effective at 3 years in 92.6% of the bootstrap replications. After 5 years, average total costs were 81,790 dollars for PCI versus 100,522 dollars for CABG patients, a difference of 18,732 dollars (95% CI 9873 dollars to 27,831 dollars), whereas survival at 5 years was 0.75 for PCI patients versus 0.70 for CABG patients (P=0.21). At 5 years, PCI remained less costly and more effective in 89.4% of the bootstrap replications.PCI was less costly and at least as effective for the urgent revascularization of medically refractory, high-risk patients over 5 years.
A Novel Epigenetic Phenotype Associated With the Most Aggressive Pathway of Bladder Tumor Progression
Authors: Céline Vallot, Nicolas Stransky, Isabelle Bernard-Pierrot, Aurélie Hérault, Jessica Zucman-Rossi, Elodie Chapeaublanc, Dimitri Vordos, Agnès Laplanche, Simone Benhamou, Thierry Lebret, Jennifer Southgate, Yves Allory, François Radvanyi
Journal: JNCI Journal of the National Cancer Institute (2010)

Epigenetic silencing can extend to whole chromosomal regions in cancer. There have been few genome-wide studies exploring its involvement in tumorigenesis. We searched for chromosomal regions affected by epigenetic silencing in cancer by using Affymetrix microarrays and real-time quantitative polymerase chain reaction to analyze RNA from 57 bladder tumors compared with normal urothelium. Epigenetic silencing was verified by gene re-expression following treatment of bladder cell lines with 5-aza-deoxycytidine, a DNA demethylating agent, and trichostatin A, a histone deacetylase inhibitor. DNA methylation was studied by bisulfite sequencing and histone methylation and acetylation by chromatin immunoprecipitation. Clustering was used to distinguish tumors with multiple regional epigenetic silencing (MRES) from those without and to analyze the association of this phenotype with histopathologic and molecular types of bladder cancer. The results were confirmed with a second panel of 40 tumor samples and extended in vitro with seven bladder cancer cell lines. All statistical tests were two-sided. We identified seven chromosomal regions of contiguous genes that were silenced by an epigenetic mechanism. Epigenetic silencing was not associated with DNA methylation but was associated with histone H3K9 and H3K27 methylation and histone H3K9 hypoacetylation. All seven regions were concordantly silenced in a subgroup of 26 tumors, defining an MRES phenotype. MRES tumors exhibited a carcinoma in situ–associated gene expression signature (25 of 26 MRES tumors vs 0 of 31 non-MRES tumors, P < 10−14), rarely carried FGFR3 mutations (one of 26 vs 22 of 31 non-MRES tumors, P < 10−6), and contained 25 of 33 (76%) of the muscle-invasive tumors. Cell lines derived from aggressive bladder tumors presented epigenetic silencing of the same regions. We have identified an MRES phenotype characterized by the concomitant epigenetic silencing of several chromosomal regions, which, in bladder cancer, is specifically associated with the carcinoma in situ gene expression signature.
Cooperation of C/EBP family proteins and chromatin remodeling proteins is essential for termination of liver regeneration
Authors: Jingling Jin, Il‐Hwa Hong, Kyle Lewis, Polina Iakova, Meghan Breaux, Yanjun Jiang, Emily Sullivan, Nicole Jawanmardi, Lubov Timchenko, Nikolai A. Timchenko
Journal: Hepatology (2014)

Liver cancer is the fifth most common cancer. A highly invasive surgical resection of the liver tumor is the main approach used to eliminate the tumor. Mechanisms that terminate liver regeneration when the liver reaches the original size are not known. The aims of this work were to generate an animal model that fails to stop liver regeneration after surgical resections and elucidate mechanisms that are involved in termination of liver regeneration. Because epigenetic control of liver function has been previously implicated in the regulation of liver proliferation, we generated C/EBPα‐S193A knockin mice, which have alterations in formation of complexes of C/EBP family proteins with chromatin remodeling proteins. The C/EBPα‐S193A mice have altered liver morphology and altered liver function leading to changes of glucose metabolism and blood parameters. Examination of the proliferative capacity of C/EBPα‐S193A livers showed that livers of S193A mice have a higher rate of proliferation after birth, but stop proliferation at the age of 2 months. These animals have increased liver proliferation in response to liver surgery as well as carbon tetrachloride (CCl 4 )‐mediated injury. Importantly, livers of C/EBPα‐S193A mice fail to stop liver regeneration after surgery when livers reach the original, preresection, size. The failure of S193A livers to stop regeneration correlates with the epigenetic repression of key regulators of liver proliferation C/EBPα, p53, FXR, SIRT1, PGC1α, and TERT by C/EBPβ‐HDAC1 complexes. The C/EBPβ‐HDAC1 complexes also repress promoters of enzymes of glucose synthesis PEPCK and G6Pase. Conclusion : Proper cooperation of C/EBP and chromatin remodeling proteins is essential for the termination of liver regeneration after surgery and for maintenance of liver functions. (H epatology 2015;61:315–325)
Inhomogeneous Disappearance of Myofilament-Related Cytoskeletal Proteins in Stunned Myocardium of Guinea Pig
Authors: Yasushi Matsumura, Eijiro Saeki, Michitoshi Inoue, Masatsugu Hori, Takenobu Kamada, Hideo Kusuoka
Journal: Circulation Research (1996)

The decrease in Ca 2+ responsiveness of myofilaments in stunned myocardium implies that there may be structural changes in proteins composing the contractile machinery. To elucidate the lesion in stunned myocardium, isolated guinea pig hearts were subjected to global ischemia at 37°C and reperfused. SDS-PAGE revealed that the contents of desmin, α-actinin, and spectrin decreased in the myofibrillar fraction isolated from hearts reperfused after 60-minute ischemia compared with nonischemic control hearts. To examine the change of cytoskeletal proteins in stunned myocardium, immunohistochemical studies with antibodies against these proteins were performed after 15 minutes of ischemia. In stunned myocardium, the staining was largely intact, but there were some lesions where desmin was not stained and α-actinin and spectrin were only weakly identified. The percentage of normally stained areas in the myocardium (percent stained area), quantified by image processing, was significantly lower in stunned myocardium (79.6±3.6%, mean±SEM) than in nonischemic control myocardium (96.5±0.7%). Percent recovery of developed pressure significantly correlated with percent stained area ( r =.82, P &lt;.001). In hearts subjected to 15-minute ischemia but not reperfused, or in hearts reperfused with Ca 2+ -free solution after 15-minute ischemia, staining by the antibodies remained intact, suggesting that the change of the cytoskeletal proteins is mediated by Ca 2+ overload during reperfusion. In hearts treated with the protease inhibitor leupeptin (50 μmol/L) or calpain inhibitor I (100 μmol/L), both developed pressure and staining were well preserved. These results indicate that contractile dysfunction in stunned myocardium has a strong correlation with the disappearance of cytoskeletal proteins that may be mediated by a Ca 2+ -dependent intracellular protease activated during reperfusion. The disruption of cytoskeletal proteins is a possible mechanism for stunning, although it may be a secondary effect of protease activation.
Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study
Authors: Karla C.L. Lee, Luisa A. Baker, Giacomo Stanzani, Hatim Alibhai, Yu Mei Chang, Carolina Jimenez Palacios, Pamela J. Leckie, Paola Giordano, Simon L. Priestnall, Daniel J. Antoine, Rosalind E. Jenkins, Christopher E. Goldring, B. Kevin Park, Fausto Andreola, Banwari Agarwal, Rajeshwar P. Mookerjee, Nathan A. Davies, Rajiv Jalan
Journal: Journal of Hepatology (2015)

Graphical abstractAbstractBackground & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients.
On the Rate of Formation of Steroidal Glucuronosides in Patients with Familial and Acquired Jaundice*
Authors: William D. Drucker, Anastasia Sfikakis, Abraham J. Borkowski, Nicholas P. Christy
Journal: Journal of Clinical Investigation (1964)

The inactivation and excretion of many lipid- soluble compounds is a result of metabolic trans- formation to more polar substances (1).For cor- tisol,1 this is sequentially accomplished in man by reduction of the 4,5 double bond in ring A to yield "dihydro" derivatives, then reduction of the ke- tone group at carbon three to yield "tetrahydro" compounds (2).Reduction of the C-20 ketone group to a hydroxyl leads to further increase in polarity (3).Once formed, these reduced com- pounds are rendered still more water-soluble by conjugation at the three position with glucuronic acid (1, 4).The formation of such glucurono- sides also results in a lesser degree of binding to plasma proteins (5,6).The conjugation of a substrate with glucuronic acid in ester or glycosidic linkage requires uridine