tbuckley/cabot-search huggingface dataset:
Leukotriene B4 release by human lung macrophages via receptor- not voltage-operated Ca2+ channels
Authors: T. K. Finney-Hayward, P. Bahra, S. Li, C. T. Poll, A. G. Nicholson, R. E. K. Russell, P. A. Ford, J. Westwick, P. S. Fenwick, P. J. Barnes, L. E. Donnelly
Journal: European Respiratory Journal (2009)

Increased numbers of macrophages and neutrophils in the lung is a key feature of chronic obstructive pulmonary disease (COPD). The major neutrophil chemotactic agent in the airways of COPD patients is leukotriene (LT)B 4 and is released by macrophages. The present study examines the role and mechanism of Ca 2+ in platelet-activating factor (PAF)-stimulated LTB 4 release from human lung macrophages. Macrophages were isolated from lung tissue of subjects undergoing lung resection surgery and monocyte-derived macrophages (MDM) were obtained from nonsmokers, smokers without obstruction and COPD patients. Cells were stimulated with PAF and LTB 4 release and [Ca 2+ ] i was measured. Lung macrophages and MDM released LTB 4 following stimulation with PAF (mean effective concentration: 0.08±0.06 μM (n = 5) versus 0.17±0.12 μM (n = 17), respectively). Compared with MDM, lung macrophages released approximately eight-fold more LTB 4 . Neither smoking nor COPD altered MDM responses. PAF-stimulated LTB 4 release was abrogated by ethylene glycol tetraacetic acid suggesting a role for extracellular Ca 2+ . This was substantiated by using store-operated channel blockers econazole, SK&amp;F96365 and Gd 3+ . However, econazole and SK&amp;F96365 were more effective in MDM than lung macrophages. Neither LOE908 nor nifedipine could attenuate this response. These data suggest that platelet-activating factor-stimulated leukotriene B 4 release from human lung macrophages is mediated, in part, by Ca 2+ influx through receptor- but not voltage-operated Ca 2+ channels.
Carboplatin and cisplatin pharmacokinetics after intrapleural combination treatment in patients with malignant pleural effusion
Authors: R. Lerza, M.O. Vannozzi, G. Tolino, M. Viale, G.B. Bottino, G. Bogliolo, A. Cerruti, G. Castello, M. Mencoboni, G. Reggiardo, I. Pannacciulli, M. Esposito
Journal: Annals of Oncology (1997)
Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia
Authors: Yasunori Sawayama, Chie Shimizu, Naoyasu Maeda, Masafumi Tatsukawa, Naoko Kinukawa, Samon Koyanagi, Seizaburo Kashiwagi, Jun Hayashi
Journal: Journal of the American College of Cardiology (2002)
Effects of cardioselective beta blockade on the peripheral lung in guinea pigs
Authors: C Clerici, I Macquin-Mavier, A Harf
Journal: European Respiratory Journal (1988)

Impairment of lung function with selective beta-1 blocking drugs has been repeatedly demonstrated in guinea pigs, normal subjects and asthmatic patients. The effects of several beta blockers, propranolol (non-selective), atenolol (beta-1 selective), IPS 339 (beta-2 selective) on histamine-induced bronchoconstriction have been investigated in 30 anaesthetized and mechanically ventilated guinea pigs, measuring changes in conductance and dynamic compliance. Their effects on peripheral lung, where only beta-2 adrenoceptors are present, were more specifically assessed using changes in lung distensibility by means of static pressure-volume curves. Atenolol (1 mg.kg-1), IPS 339 (2 mg.kg-1) and propranolol (2 mg.kg-1) enhanced histamine-induced decrease in lung distensibility, conductance and dynamic compliance. The decrease was of the same order of magnitude for all three parameters. Atenolol (1 mg.kg-1) and propranolol (2 mg.kg-1) decreased lung distensibility to the same extent. By contrast low dose atenolol (0.1 mg.kg-1) did not potentiate histamine-induced bronchoconstriction although this dose did produce a significant cardiac beta blockade. These results demonstrate that 1) beta blockers have a clear effect on the peripheral lung, 2) beta-1 adrenoceptors are not involved in pulmonary effects of cardioselective drugs. They suggest that dose dependent loss of selectivity is the major mechanism behind impairment of lung function following such drugs.
Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat.
Authors: M G Seikaly, B S Arant, F D Seney
Journal: Journal of Clinical Investigation (1990)

To examine angiotensin (ANG) concentrations in fluid compartments near known intrarenal ANG receptors, we measured ANG concentrations in glomerular filtrate (GF), star vessel plasma (SVP), and luminal fluid from the early, mid, and late proximal tubule (E, M, and L PT). Samples were collected from euvolemic Munich-Wistar rats by free-flow micropuncture; ANG concentrations were measured by RIA. In one group of rats, concentrations of total immunoreactive ANG (reflecting ANG II and lesser amounts of three fragments) in GF and E, M, and L PT fluid averaged 29-40 nM compared with 32 pM in systemic plasma. In a second group, immunoreactive ANG concentrations in SVP also exceeded systemic levels by a factor of 1,000. In a final group, samples of GF and LPT fluid were purified by HPLC before RIA to measure ANG II and III concentrations specifically: their respective concentrations were 6-8 nM and 14-25 nM. We interpret these results to indicate that substantial amounts of ANG peptides are released into or generated within intrarenal fluid compartments, in which local ANG is likely to effect regulation of renal function independently of systemic ANG.
Influence of Cellular Ganglioside Depletion on Tumor Formation
Authors: W. Deng
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Gangliosides are immunosuppressive cell surface molecules that are often present in high concentrations in and shed actively by tumor cells. These molecules inhibit the antitumor immune response that is implicated in tumor rejection. We therefore determined the ability of tumor cells pharmacologically depleted of gangliosides to form tumors in mice. Methods: We tested a ganglioside-rich subline of B16 murine melanoma, MEB4, and MEB4 cells that had been depleted of endogenous gangliosides by incubation with 0.5 μM 1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol, a specific inhibitor of the enzyme glucosylceramide synthase. Tumor formation was assessed twice a week for 10 weeks after the intradermal injection of tumor cells, and metastatic potential was assessed 4 weeks after tail vein injection of tumor cells. All P values are from two-sided tests. Results: Reduction of the ganglioside content of MEB4 cells, which was not cytotoxic to cells and did not inhibit cell proliferation in vitro, markedly reduced their ability to form tumors. Only 40% of the mice given an intradermal injection of 105 ganglioside-depleted MEB4 cells developed tumors compared with 100% of the mice given an injection of 105 control MEB4 cells (P<.001). Ganglioside depletion also reduced metastasis: A mean of five pulmonary metastases was detected per mouse given an injection of 2 × 105 ganglioside-depleted MEB4 cells compared with a mean of 25 per mouse given an injection of 2 × 105 control MEB4 cells. Conclusion: Tumor cells with a pharmacologically decreased concentration of gangliosides produce fewer tumors in mice than do untreated cells, suggesting that pharmacologic depletion of gangliosides should be explored further as a therapeutic approach to cancer.
Birth weight, education, environment, and lung function at school age: a community study in an alpine area
Authors: P Lercher, R Schmitzberger
Journal: European Respiratory Journal (1997)

Our aim was to assess the effect of birth weight, gestational age, predispositions, education, housing and environmental factors on indices of lung function and to evaluate selective interactions among the main predictors. We studied schoolchildren (aged 7.5-12 yrs) in a cross-sectional survey of 13 small alpine communities in Tyrol (Austria). Data were collected retrospectively from self-administered questionnaires (n=796, 85% response), public records and lung function testing (n=752, 80% response). In the multivariate analysis it was found that a low birth weight (LBW), a low length of maternal education, a smaller gestational age, and a larger family size were all negatively associated with most lung function measures. Additionally, three significant interactions (birth weight with maternal education, birth weight with gestational age; and birth weight with family size) were observed. This implies that children of an LBW with mothers having a low level of education have a forced expiratory volume in one second (FEV1) value 148 mL lower than average values. Children born at term with an LBW have a 140 mL lower mean FEV1 value, and children of LBW from larger families display a 123 mL lower mean estimate of FEV1. However, subgroups were small (n=26, 17 and 27, respectively). The results support low birth weight as a significant predictor of decreased lung function at school age. However, the size and the direction of the association may differ depending on the levels of the interacting variables.
A dilemma of skeletal tuberculous diagnosis
Authors: Parvaneh Baghaei Shiva, Majid Marjani, Payam Tabarsi, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2012)

Objectives: Skeletal tuberculosis reports 1-5% of all TB cases. The most common sites of involvement are spine, knee and hip. The diagnosis of extra-pulmonary TB is difficult. The aim of this study was to show up the different way of diagnosis and report this kind of TB in Iran.  Method: This study was done in Masih Daneshvari Hospital, a referral center of TB in Iran, from 2003 to 2011. In this retrospective study, we extracted all skeletal TB. Demographic information, the method of diagnosis, and other information were evaluated.  Results: Of 426 extra-pulmonary TB, 58(13.6%) patients were skeletal TB. The mean age was 45.72±20.26yrs. 31(53.4%) patients were male. One patient was HIV positive. New cases of TB, relapse and history of TB treatment were 51, 4 and 3 respectively. Median of duration of symptoms was 7 months. 28 patients had pulmonary TB (sputum smear or culture was positive). The kind of skeletal TB was: 2patients with pleural, one patient with CNS, one patient with lymph node concomitant with spine and 52 patients just spine. Two patients were arthritis (knee) tuberculosis. Diagnostic method was: positive granuloma 43.7%, PCR positive 31.2%, positive smear and culture 43.7%, diagnosed by positive sputum for TB 31% and diagnosed by clinical/ magnetic resonance imaging 13.7%.  Conclusion: The diagnosis of skeletal TB is difficult and it will take time to detect it. Investigation of other involved site such as lungs, pleura or lymph nodes can help us early TB diagnosis.
Myc-Induced MicroRNAs Integrate Myc-Mediated Cell Proliferation and Cell Fate
Authors: Jong Wook Kim, Seiichi Mori, Joseph R. Nevins
Journal: Cancer Research (2010)

The Myc pathway, often deregulated in cancer, is critical in determining cell fate by coordinating a gene expression program that links the control of cell proliferation with cell fate decisions. As such, precise control of the Myc pathway activity must be achieved to ensure faithful execution of appropriate cellular response and to prevent progressing toward a malignant state. With recent highlighted roles of microRNAs (miRNA) as critical components of gene control, we sought to evaluate the extent to which miRNAs may contribute in the execution of Myc function. Combined analysis of mRNA and miRNA expression profiles reveals an integration whereby the Myc-mediated induction of miRNAs leads to the repression of various mRNAs encoding tumor suppressors that block cell proliferation including p21, p27, and Rb. In addition, the proapoptotic PTEN tumor suppressor gene is also repressed by Myc-induced miRNAs, suggesting that Myc-induced miRNAs contribute to the precise control of a transcriptional program that coordinates the balance of cell proliferation and cell death.
Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia
Authors: P. Pasricha, R. Hawari, I. Ahmed, J. Chen, P. Cotton, R. Hawes, A. Kalloo, S. Kantsevoy, C. Gostout
Journal: Endoscopy (2007)

See also: Commentaire de travail de P. J. Pasricha et al., pp. 761Endoscopy 2007; 39(09): 930-930DOI: 10.1055/s-0032-1308864
Antibody-Dependent Cell-Mediated Cytotoxicity Overcomes NK Cell Resistance in <i>MLL</i>-Rearranged Leukemia Expressing Inhibitory KIR Ligands but Not Activating Ligands
Authors: Wing Keung Chan, May Kung Sutherland, Ying Li, Jonathan Zalevsky, Sarah Schell, Wing Leung
Journal: Clinical Cancer Research (2012)

Leukemias with MLL gene rearrangement are associated with a poor prognosis. Natural killer (NK) cell therapy is a potential treatment, but leukemia cells may be resistant. Here, we sought to determine the susceptibility of MLL-rearranged leukemia cells to NK cell lysis and to develop a novel immunotherapeutic approach to optimize NK cell therapy, including the use of an antibody against leukemia-associated antigen and the elimination of killer-cell immunoglobulin-like receptor (KIR)-mediated inhibition.Three MLL-rearranged leukemia cell lines (RS4;11, SEM, and MV4-11) and primary leukemia blasts were assessed for surface phenotype and susceptibility to NK cell lysis with or without antibodies against CD19 (XmAb5574), CD33 (lintuzumab), or KIR ligands.All three cell lines were resistant to NK cell lysis, had some inhibitory KIR ligands and protease inhibitor-9, and expressed low levels of NKG2D activating ligands and adhesion molecules. After treatment with XmAb5574 or lintuzumab, MLL-rearranged leukemia cells were efficiently killed by NK cells. The addition of pan-major histocompatibility complex class I antibody, which blocked inhibitory KIR-HLA interaction, further augmented degranulation in all three KIR2DL1, KIR2DL2/3, and KIR3DL1 subsets of NK cells based on the rule of missing-self recognition. A mouse model showed a decreased rate of leukemia progression in vivo as monitored by bioluminescence imaging and longer survival after antibody treatment.Our data support the use of a triple immunotherapy approach, including an antibody directed against tumor-associated antigen, KIR-mismatched NK cell transplantation, and inhibitory KIR blockade, for the treatment of NK cell-resistant MLL-rearranged leukemias.
Expression of a Targeted λ1 Light Chain Gene Is Developmentally Regulated and Independent of Igκ Rearrangements
Authors: Philipp Oberdoerffer, Tatiana I. Novobrantseva, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (2003)

Immunoglobulin light chain (IgL) rearrangements occur more frequently at Igκ than at Igλ. Previous results suggested that the unrearranged Igκ locus negatively regulates Igλ transcription and/or rearrangement. Here, we demonstrate that expression of a VJλ1-joint inserted into its physiological position in the Igλ locus is independent of Igκ rearrangements. Expression of the inserted VJλ1 gene segment is developmentally controlled like that of a VJκ-joint inserted into the Igκ locus and furthermore coincides developmentally with the occurrence of Igκ rearrangements in wild-type mice. We conclude that developmentally controlled transcription of a gene rearrangement in the Igλ locus occurs in the presence of an unrearranged Igκ locus and is therefore not negatively regulated by the latter. Our data also indicate light chain editing in ∼30% of λ1 expressing B cell progenitors.
Pregnancy as a cardiac stress model
Authors: E. Chung, L. A. Leinwand
Journal: Cardiovascular Research (2014)

Cardiac hypertrophy occurs during pregnancy as a consequence of both volume overload and hormonal changes. Both pregnancy- and exercise-induced cardiac hypertrophy are generally thought to be similar and physiological. Despite the fact that there are shared transcriptional responses in both forms of cardiac adaptation, pregnancy results in a distinct signature of gene expression in the heart. In some cases, however, pregnancy can induce adverse cardiac events in previously healthy women without any known cardiovascular disease. Peripartum cardiomyopathy is the leading cause of non-obstetric mortality during pregnancy. To understand how pregnancy can cause heart disease, it is first important to understand cardiac adaptation during normal pregnancy. This review provides an overview of the cardiac consequences of pregnancy, including haemodynamic, functional, structural, and morphological adaptations, as well as molecular phenotypes. In addition, this review describes the signalling pathways responsible for pregnancy-induced cardiac hypertrophy and angiogenesis. We also compare and contrast cardiac adaptation in response to disease, exercise, and pregnancy. The comparisons of these settings of cardiac hypertrophy provide insight into pregnancy-associated cardiac adaptation.
Clinical trials in lung cancer: nihilism versus enthusiasm
Authors: S. G. Spiro
Journal: Thorax (1997)

In the mid 1950s Roger Altounyan began work Small cell lung cancer I will first summarise some important points on a natural compound, khellin, the active constituent of an Eastern Mediterranean plant, learnt from the work of our group and of others in SCLC and will then proceed to discuss Ammi visnaga, which had been known since Biblical times to have bronchodilator prop-the difficulties we have in transforming this approach to the much more common con-erties.However, its side effects outweighed any potential beneficial effects and the project was stellation of lung cancers that comprise NSCLC.abandoned until 1964 when it was reinstated under Fison's management.By 1965 Al-Figure 1 summarises the studies that the London Lung Cancer Group have carried out tounyan had identified sodium cromoglycate as a potential substance protective against asthma in small cell lung cancers.I shall comment briefly on the value of the addition of radio-(but not a bronchodilator) with sufficiently long duration of action to be clinically useful.Roger, therapy to chemotherapy in SCLC, the optimum duration of chemotherapy, and the being asthmatic, tested this and most other possible compounds on himself.Clinical trials intensification of chemotherapy, including our studies on high dose chemotherapy and also with cromoglycate began soon afterwards. Department ofMy own interest in clinical trials provided the the recent studies of less intensive chemo-Thoracic Medicine, stimulus for the establishment of the London therapy with oral etoposide in patients with aThe Middlesex Hospital, Lung Cancer Group in 1979.Over the next poorer prognosis.
Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies
Authors: P. J. Castaldi, D. L. Demeo, C. P. Hersh, D. A. Lomas, I. C. Soerheim, A. Gulsvik, P. Bakke, S. Rennard, P. Pare, J. Vestbo, E. K. Silverman
Journal: Thorax (2010)

<h3>Background</h3> The identification of gene-by-environment interactions is important for understanding the genetic basis of chronic obstructive pulmonary disease (COPD). Many COPD genetic association analyses assume a linear relationship between pack-years of smoking exposure and forced expiratory volume in 1 s (FEV<sub>1</sub>); however, this assumption has not been evaluated empirically in cohorts with a wide spectrum of COPD severity. <h3>Methods</h3> The relationship between FEV<sub>1</sub> and pack-years of smoking exposure was examined in four large cohorts assembled for the purpose of identifying genetic associations with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects. <h3>Results</h3> Non-linear relationships between smoking and FEV<sub>1</sub> were identified in the four cohorts. It was found that, in most situations where the relationship between pack-years and FEV<sub>1</sub> is non-linear, a piecewise linear approach to model smoking and gene-by-smoking interactions is preferable to the commonly used total pack-years approach. The piecewise linear approach was applied to a genetic association analysis of the PI*Z allele in the Norway Case–Control cohort and a potential PI*Z-by-smoking interaction was identified (p=0.03 for FEV<sub>1</sub> analysis, p=0.01 for COPD susceptibility analysis). <h3>Conclusion</h3> In study samples of subjects with a wide range of COPD severity, a non-linear relationship between pack-years of smoking and FEV<sub>1</sub> is likely. In this setting, approaches that account for this non-linearity can be more powerful and less biased than the more common approach of using total pack-years to model the smoking effect.
Aberrant “Default Mode” Functional Connectivity in Schizophrenia
Authors: Abigail G. Garrity, Godfrey D. Pearlson, Kristen McKiernan, Dan Lloyd, Kent A. Kiehl, Vince D. Calhoun
Journal: American Journal of Psychiatry (2007)

Objective: The “default mode” has been defined as a baseline condition of brain function and is of interest because its component brain regions are believed to be abnormal in schizophrenia. It was hypothesized that the default mode network would show abnormal activation and connectivity in patients with schizophrenia. Method: Patients with schizophrenia (N=21) and healthy comparison subjects (N=22) performed an auditory oddball task during functional magnetic resonance imaging (fMRI). Independent component analysis was used to identify the default mode component. Differences in the spatial and temporal aspects of the default mode network were examined in patients versus comparison subjects. Results: Healthy comparison subjects and patients had significant spatial differences in the default mode network, most notably in the frontal, anterior cingulate, and parahippocampal gyri. In addition, activity in patients in the medial frontal, temporal, and cingulate gyri correlated with severity of positive symptoms. The patients also showed significantly higher frequency fluctuations in the temporal evolution of the default mode. Conclusions: Schizophrenia is associated with altered temporal frequency and spatial location of the default mode network. The authors hypothesized that this network may be under- or overmodulated by key regions, including the anterior and posterior cingulate cortex. In addition, the altered temporal fluctuations in patients may result from a change in the connectivity of these regions with other brain networks.
Meningiomas in children and adolescents: a meta-analysis of individual patient data
Authors: Rishi S Kotecha, Elaine M Pascoe, Elisabeth J Rushing, Lucy B Rorke-Adams, Ted Zwerdling, Xing Gao, Xin Li, Stephanie Greene, Abbas Amirjamshidi, Seung-Ki Kim, Marco A Lima, Po-Cheng Hung, Fayçal Lakhdar, Nirav Mehta, Yuguang Liu, B Indira Devi, B Jayanand Sudhir, Morten Lund-Johansen, Flemming Gjerris, Catherine H Cole, Nicholas G Gottardo
Journal: The Lancet Oncology (2011)