tbuckley/cabot-search huggingface dataset:
Expression and Activity of pH-regulatory Glutaminase in the Human Airway Epithelium
Authors: JOHN F. HUNT, ELIZABETH ERWIN, LISA PALMER, JOHN VAUGHAN, NEIL MALHOTRA, THOMAS A. E. PLATTS-MILLS, BENJAMIN GASTON
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media pH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon- γ and tumor necrosis factor- α . Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 μ M [range: 0–233], n = 18, age 23 ± 2.5 yr) compared with control subjects (327 μ M [14–1,220], n = 24, age 24 ± 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation.
Interplay Between Mitral Regurgitation and Transcatheter Aortic Valve Replacement With the CoreValve Revalving System
Authors: Francesco Bedogni, Azeem Latib, Federico De Marco, Mauro Agnifili, Jacopo Oreglia, Samuele Pizzocri, Roberto A. Latini, Stefania Lanotte, Anna Sonia Petronio, Marco De Carlo, Federica Ettori, Claudia Fiorina, Arnaldo Poli, Silvia Cirri, Stefano De Servi, Angelo Ramondo, Giuseppe Tarantini, Antonio Marzocchi, Rosario Fiorilli, Silvio Klugmann, Gian Paolo Ussia, Corrado Tamburino, Francesco Maisano, Nedy Brambilla, Antonio Colombo, Luca Testa
Journal: Circulation (2013)

Background— Little is known of the prognostic significance of mitral regurgitation (MR) on transcatheter aortic valve replacement (TAVR), the impact of TAVR on MR severity, and the variables associated with possible post-TAVR improvement in MR. We evaluated these issues in a multicenter registry of patients undergoing CoreValve Revalving System–TAVR. Methods and Results— Among 1007 consecutive patients, 670 (66.5%), 243 (24.1%), and 94 (9.3%) presented with no/mild, moderate, and severe MR, respectively. At 1 month after TAVR, patients with severe or moderate MR showed comparable mortality rates (odds ratio, 1.1; 95% confidence interval [95% CI], 0.7–1.55; P =0.2), but both were significantly higher compared with patients with mild/no MR (odds ratio, 2.2; 95% CI, 1.78–3.28; P &lt;0.001; and odds ratio, 1.9; 95% CI, 1.1–3.3; P =0.02, respectively). One-year mortality was also similar between patients with severe and those with moderate MR (hazard ratio, 1.4; 95% CI, 0.94–2.4; P =0.06) and still significantly higher compared with patients with mild/no MR (hazard ratio, 1.7; 95% CI, 1.2–3.41; P &lt;0.001; and hazard ratio, 1.4; 95% CI, 1.2–2.2; P =0.03, respectively). Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but not an improvement of ≥1 grade in MR severity, were independent predictors of mortality at 1 year. At 1 year, an improved MR was observed in 47% and 35% of patients with severe and moderate MR, respectively. The rate of low implantation was consistent across groups with improved, unchanged, or worsened MR. A functional type of MR and the absence of severe pulmonary hypertension and atrial fibrillation independently predicted the improvement in MR severity. Conclusions— Baseline MR greater than mild is associated with higher mortality after CoreValve Revalving System–TAVR. A significant improvement in MR was more likely in patients with functional MR and without severe pulmonary hypertension or atrial fibrillation. The improvement in MR did not independently predict mortality.
Sustained effector function of IL-12/15/18–preactivated NK cells against established tumors
Authors: Jing Ni, Matthias Miller, Ana Stojanovic, Natalio Garbi, Adelheid Cerwenka
Journal: The Journal of Experimental Medicine (2012)

Natural killer cell (NK cell)–based immunotherapy of cancer is hampered by the transient effector function of NK cells. Recently, mouse IL-12/15/18–preactivated NK cells were shown to persist with sustained effector function in vivo. Our study investigated the antitumor activity of such NK cells. A single injection of syngeneic IL-12/15/18–preactivated NK cells, but neither naive nor IL-15– or IL-2–pretreated NK cells, combined with irradiation substantially reduced growth of established mouse tumors. Radiation therapy (RT) was essential for the antitumor activity of transferred NK cells. IL-12/15/18–preactivated NK cells expressed high levels of IL-2Rα (CD25), and their rapid in vivo proliferation depended on IL-2 produced by CD4+ T cells. IL-12/15/18–preactivated NK cells accumulated in the tumor tissue and persisted at high cell numbers with potent effector function that required the presence of CD4+ T cells. RT greatly increased numbers and function of transferred NK cells. Human IL-12/15/18–preactivated NK cells also displayed sustained effector function in vitro. Our study provides a better understanding for the rational design of immunotherapies of cancer that incorporate NK cells. Moreover, our results reveal an essential role of CD4+ T cell help for sustained antitumor activity by NK cells linking adaptive and innate immunity.
The importance of ultrasound in staging and gaining a pathological diagnosis in patients with lung cancer--a two year single centre experience
Authors: M. M. Hoosein, D. Barnes, A. N. Khan, M. D. Peake, J. Bennett, D. Purnell, C. Free, J. J. Entwisle
Journal: Thorax (2011)

Initial studies on the use of ultrasound in the detection and sampling of supraclavicular lymph nodes in patients with suspected lung cancer show this to be a promising technique, giving both a cytological diagnosis and pathological N3 (pN3) stage. Leicester published its initial experience in 2005 and the aim of this study was to establish if this had been embedded into the diagnostic pathway, and further to examine the use of ultrasound in diagnosing and staging lung cancer by imaging other areas including pleural effusions, chest wall, bone and liver lesions.All patients diagnosed with lung cancer, registered on the Leicester lung cancer database over a two year period between January 2007 and December 2008, had their imaging and pathology retrospectively reviewed; 996 primary lung cancer patients were identified (n=996). Of these, 318 patients underwent an ultrasound examination (n=318), consisting of ultrasound of the neck, pleural cavity, and metastatic lesions potentially amenable to ultrasound guided aspiration/biopsy.The overall malignant yield was 45% of patients scanned (95% CI 39.5% to 50.4%) and 81.3% of patients sampled (95% CI 75.5% to 87%). Of the 996 patients, 14.4% (n=143) had a positive ultrasound guided cytological diagnosis (95% CI 12.2% to 16.5%). Of all the pathological diagnoses (n=765), 18.7% were ultrasound guided (95% CI 15.9% to 21.5%). In particular, 32.2% of patients with CT detected neck or mediastinal nodes had a diagnosis and stage achieved by neck ultrasound.The use of ultrasound gives a rapid and less invasive method of diagnosing and staging lung cancer and has become embedded into the diagnostic pathway. We advocate its increased use and availability in patients with lung cancer.
Altered Ion Transport in Vascular Smooth Muscle from Spontaneously Hypertensive Rats
Authors: ALLAN W. JONES
Journal: Circulation Research (1973)

The interaction of vascular electrolytes and early spontaneous hypertension was studied in the rat aorta. Chemical composition (H 2 O, Na, K, Ca, Mg, Cl, collagen, and elastin), extracellular space, and cell water content were little changed. Only uronic acid and hexosamine contents were significantly elevated in the spontaneously hypertensive rat. Approximately 37% of the aortic weight was cellular. Functional changes in ion transport were observed in smooth muscle from hypertensive rats; the muscle exhibited decreased ability to accumulate K and extrude Na and increased turnover of 42 K (0.0165 ± 0.0009 vs. 0.0086 ± 0.0002 min -1 ) and 36 C1 (0.162 ± 0.011 vs. 0.118 ± 0.003 min -1 ). Spontaneously hypertensive rats maintained increased 42 K exchange after adrenalectomy and reserpinization. The bioregulants, aldosterone, norepinephrine, and angiotensin had important actions on ion exchange. After adrenalectomy, aldosterone therapy reduced 42 K exchange toward intact levels. Norepinephrine increased the rate of 42 K exchange with the dose-response relation having a lower median effective dose (ED 50 ) for spontaneously hypertensive rats (10 -9 g/ml) than it did for normal Wistar rats (2 x 10 -9 g/ml). Angiotensin also increased 42 K exchange with similar dose-response relations for both groups. I concluded that functional alterations observed in spontaneously hypertensive rats probably resulted from primary changes in ion transport by vascular smooth muscle rather than from secondary effects of altered regulatory systems. The decreased selectivity to K over Na and the increased turnover of ions could lead to increased reactivity to norepinephrine through effects on membrane potentials.
195 RIFAXIMIN DECREASES VENOUS AMMONIA CONCENTRATIONS AND TIME-WEIGHTED AVERAGE AMMONIA CONCENTRATIONS CORRELATE WITH OVERT HEPATIC ENCEPHALOPATHY (HE) AS ASSESSED BY CONN SCORE IN A 6-MONTH STUDY
Authors: A. Sanyal, N. Bass, F. Poordad, M.Y. Sheikh, K. Mullen, S. Sigal, T. Frederick, R. Brown, B. Bhandari, S. Sedghi, K. Merchant, S. Huang, A. Shaw, E. Bortey, W.P. Forbes
Journal: Journal of Hepatology (2010)
Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?
Authors: C D Schwindt, F Zaldivar, L Wilson, S-Y Leu, J Wang-Rodriguez, P J Mills, D M Cooper
Journal: British Journal of Sports Medicine (2006)

Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses.To determine whether (1) a 6-min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma.Children with mild-moderate persistent asthma and age-matched controls (n = 14 in each group, mean age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry.Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma, 1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl; children with asthma, 88 (20) cells/microl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl; children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these cell types was found in children with asthma.Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilizes circulating immune cells.
Concentrated ambient air particles induce vasoconstriction of small pulmonary arteries in rats.
Authors: Joao R F Batalha, Paulo H N Saldiva, Robert W Clarke, Brent A Coull, Rebecca C Stearns, Joy Lawrence, G G Krishna Murthy, Petros Koutrakis, John J Godleski
Journal: Environmental Health Perspectives (2002)

The objective of this study was to determine whether short-term exposures to concentrated ambient particles (CAPs) alter the morphology of small pulmonary arteries in normal rats and rats with chronic bronchitis (CB). Sprague-Dawley male rats were exposed to CAPs, using the Harvard Ambient Particle Concentrator, or to particle-free air (sham) under identical conditions during 3 consecutive days (5 hr/day) in six experimental sets. CB was induced by exposure to 276 +/- 9 ppm of sulfur dioxide (5 hr/day, 5 days/week, 6 weeks). Physicochemical characterization of CAPs included measurements of particle mass, size distribution, and composition. Rats were sacrificed 24 hr after the last CAPs exposure. Histologic slides were prepared from random sections of lung lobes and coded for blinded analysis. The lumen/wall area (L/W) ratio was determined morphometrically on transverse sections of small pulmonary arteries. When all animal data (normal and CB) were analyzed together, the L/W ratios decreased as concentrations of fine particle mass, silicon, lead, sulfate, elemental carbon, and organic carbon increased. In separate univariate analyses of animal data, the association for sulfate was significant only in normal rats, whereas silicon was significantly associated in both CB and normal rats. In multivariate analyses including all particle factors, the association with silicon remained significant. Our results indicate that short-term CAPs exposures (median, 182.75 micro g/m3; range, 73.50-733.00 micro g/m3) can induce vasoconstriction of small pulmonary arteries in normal and CB rats. This effect was correlated with specific particle components and suggests that the pulmonary vasculature might be an important target for ambient air particle toxicity.
Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study
Authors: Luis Paz-Ares, Jörg Mezger, Tudor E Ciuleanu, Jürgen R Fischer, Joachim von Pawel, Mariano Provencio, Andrzej Kazarnowicz, György Losonczy, Gilberto de Castro, Aleksandra Szczesna, Lucio Crino, Martin Reck, Rodryg Ramlau, Ernst Ulsperger, Christian Schumann, Jose Elias A Miziara, Álvaro E Lessa, Mircea Dediu, Beatrix Bálint, Henrik Depenbrock, Victoria Soldatenkova, Raffael Kurek, Fred R Hirsch, Nick Thatcher, Mark A Socinski
Journal: The Lancet Oncology (2015)
Significance of pulmonary computed tomography at diagnosis in Wilms' tumor.
Authors: J A Wilimas, E C Douglass, H L Magill, S Fitch, H O Hustu
Journal: Journal of Clinical Oncology (1988)

Pulmonary lesions were found by computed tomography (CT) despite normal chest roentgenograms (CXR) at diagnosis in 11 of 124 patients with Wilms' tumor. All patients were entered on a treatment protocol at St Jude Children's Research Hospital from 1978 to 1986. The 11 patients all had favorable histology Wilms' tumor. Staging and therapy were based on interpretation of the CXR and abdominal findings. Excluding CT findings, one patient had stage I disease, two stage II, seven stage III, and one stage IV on the basis of multiple liver metastases. Four patients have relapsed: one with stage II and three with stage III. All relapses have been pulmonary. Overall, 4/11 (36%) relapsed. This relapse rate is considerably greater than the 20% overall relapse rate of patients treated according to this protocol though not statistically significant. These relapses suggest that such patients may be at increased risk for pulmonary recurrence. The results also indicate that small lesions initially noted only on CT scans of the chest in children with Wilms' tumor frequently represent metastatic tumor. Further studies of larger numbers of patients will be necessary to confirm these findings.
Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index
Authors: Shahrad Taheri, Ling Lin, Diane Austin, Terry Young, Emmanuel Mignot
Journal: PLoS Medicine (2004)

Background Sleep duration may be an important regulator of body weight and metabolism. An association between short habitual sleep time and increased body mass index (BMI) has been reported in large population samples. The potential role of metabolic hormones in this association is unknown. Methods and Findings Study participants were 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders. Participants underwent nocturnal polysomnography and reported on their sleep habits through questionnaires and sleep diaries. Following polysomnography, morning, fasted blood samples were evaluated for serum leptin and ghrelin (two key opposing hormones in appetite regulation), adiponectin, insulin, glucose, and lipid profile. Relationships among these measures, BMI, and sleep duration (habitual and immediately prior to blood sampling) were examined using multiple variable regressions with control for confounding factors. A U-shaped curvilinear association between sleep duration and BMI was observed. In persons sleeping less than 8 h (74.4% of the sample), increased BMI was proportional to decreased sleep. Short sleep was associated with low leptin (p for slope = 0.01), with a predicted 15.5% lower leptin for habitual sleep of 5 h versus 8 h, and high ghrelin (p for slope = 0.008), with a predicted 14.9% higher ghrelin for nocturnal (polysomnographic) sleep of 5 h versus 8 h, independent of BMI. Conclusion Participants with short sleep had reduced leptin and elevated ghrelin. These differences in leptin and ghrelin are likely to increase appetite, possibly explaining the increased BMI observed with short sleep duration. In Western societies, where chronic sleep restriction is common and food is widely available, changes in appetite regulatory hormones with sleep curtailment may contribute to obesity.
Making a bad thing worse: adverse effects of stress on drug addiction
Authors: Jessica N. Cleck, Julie A. Blendy
Journal: Journal of Clinical Investigation (2008)

Sustained exposure to various psychological stressors can exacerbate neuropsychiatric disorders, including drug addiction. Addiction is a chronic brain disease in which individuals cannot control their need for drugs, despite negative health and social consequences. The brains of addicted individuals are altered and respond very differently to stress than those of individuals who are not addicted. In this Review, we highlight some of the common effects of stress and drugs of abuse throughout the addiction cycle. We also discuss both animal and human studies that suggest treating the stress-related aspects of drug addiction is likely to be an important contributing factor to a long-lasting recovery from this disorder.
INTENSIVE TREATMENT OF MULTIPLE MYELOMA AND CRITERIA FOR COMPLETE REMISSION
Authors: M.E. Gore, C. Viner, M. Meldrum, J. Bell, S. Milan, A. Zuiable, M. Slevin, P.J. Selby, P.I. Clark, B. Millar, J.A. Maitland, I.R. Judson, C. Tillyer, J.S. Malpas, T.J. Mcelwain
Journal: The Lancet (1989)
Calcium and Colorectal Epithelial Cell Proliferation in Sporadic Adenoma Patients: a Randomized, Double- Blinded, Placebo-Controlled Clinical Trial
Authors: R. M. Bostick, L. Fosdick, P. Grambsch, G. A. Grandits, T. A. Louis, J. D. Potter, J. R. Wood, T. J. Lillemoe
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Calcium and Colorectal Epithelial Cell Proliferation in Sporadic Adenoma Patients: a Randomized, Double– Blinded, Placebo-Controlled Clinical Trial Get access Roberd M. Bostick, Roberd M. Bostick * Division of Epidomiology, School of Public Health and Department of Family Practice and Community Health, Medical School University of MinnesotaMinneapolis Correspondence to present address : Roberd M. Bostick, M.D., M.P.H., Department of Public Health Sciences—Epidemiology, The Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd., Winston-Salem, NC 27157. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lisa Fosdick, Lisa Fosdick Division of Biostatistics, School of Public Health, University of MinnesotaMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia Grambsch, Patricia Grambsch Division of Biostatistics, School of Public Health, University of MinnesotaMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar Greg A. Grandits, Greg A. Grandits Division of Biostatistics, School of Public Health, University of MinnesotaMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas A. Louis, Thomas A. Louis Division of Biostatistics, School of Public Health, University of MinnesotaMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Potter, John D. Potter Division of Epidemiology, School of Public Health, University of MinnesotaMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar James R. Wood, James R. Wood Digestive Healthcare, PAMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar Tamera J. Lillemoe Tamera J. Lillemoe Abbott-Northwestern HospitalMinneapolis. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 17, 6 September 1995, Pages 1307–1315, https://doi.org/10.1093/jnci/87.17.1307 Published: 06 September 1995
Polyphyletic Origin of Cultivated Rice: Based on the Interspersion Pattern of SINEs
Authors: Chaoyang Cheng, Reiko Motohashi, Suguru Tsuchimoto, Yoshimichi Fukuta, Hisako Ohtsubo, Eiichi Ohtsubo
Journal: Molecular Biology and Evolution (2003)

The wild rice species Oryza rufipogon with wide intraspecific variation is thought to be the progenitor of the cultivated rice species Oryza sativa with two ecotypes, japonica and indica. To determine the origin of cultivated rice, subfamily members of the rice retroposon p-SINE1, which show insertion polymorphism in the O. sativa -O. rufipogon population, were identified and used to "bar code" each of 101 cultivated and wild rice strains based on the presence or absence of the p-SINE1 members at the respective loci. A phylogenetic tree constructed based on the bar codes given to the rice strains showed that O. sativa strains were classified into two groups corresponding to japonica and indica, whereas O. rufipogon strains were in four groups, in which annual O. rufipogon strains formed a single group, differing from the perennial O. rufipogon strains of the other three groups. Japonica strains were closely related to the O. rufipogon perennial strains of one group, and the indica strains were closely related to the O. rufipogon annual strains, indicating that O. sativa has been derived polyphyletically from O. rufipogon. The subfamily members of p-SINE1 constitute a powerful tool for studying the classification and relationship of rice strains, even when one has limited knowledge of morphology, taxonomy, physiology, and biochemistry of rice strains.