tbuckley/cabot-search huggingface dataset:
Inhibition of cPLA<sub>2</sub>Translocation and Leukotriene C<sub>4</sub>Secretion by Fluticasone Propionate in Exogenously Activated Human Eosinophils
Authors: AKIKO SANO, NILDA M. MUÑOZ, HIROYUKI SANO, JOHN CHOI, XIANGDONG ZHU, BENJAMIN JACOBS, ALAN R. LEFF
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We examined the effect of the highly lipophilic corticosteroid, fluticasone propionate (FP), in causing (1) inhibition of nuclear translocation of cytosolic phospholipase A2 (cPLA2), and (2) blockade of leukotriene C4 (LTC4) synthesis in isolated human eosinophils in vitro. Eosinophils were isolated from peripheral blood, treated with either buffer or 10− 10 M to 10− 6 M FP in the presence of 10 pg/ml human recombinant interleukin-5 (rhIL-5) and activated with formyl-met-leu-phe (FMLP) + cytochalasin B (CB). At 24 h, stimulated LTC4 secretion from eosinophils was unchanged; however, when corrected for cell viability, LTC4 secretion decreased from 1,429 ± 327 pg/106 cells to 762 ± 113 pg/106 cells for eosinophils treated for 48 h with ⩾ 10− 8 M FP (p < 0.003). FMLP/CB-stimulated translocation of cPLA2 to the nuclear envelope assessed by specific immunohistochemical staining also was blocked by FP. By contrast, membrane expression of annexin-1, which was not minimal at 30 min, was substantial at 48 h for eosinophils treated with > 10− 10 M FP, and inhibition of LTC4 synthesis was reversed by exogenous arachidonic acid (AA). We find that FP causes a decrease in stimulated eosinophil secretion of LTC4 that is regulated by phospholipase A2 (PLA2). Inhibition of LTC4 synthesis precedes the global cytotoxic effects of FP as indicated by the simultaneous upregulation of annexin-1 expression. Inhibited stimulated secretion corresponds to inhibited translocation of cPLA2 to the nuclear envelope during cellular activation.
Genome-Wide Analysis of Selection on the Malaria Parasite Plasmodium falciparum in West African Populations of Differing Infection Endemicity
Authors: Victor A. Mobegi, Craig W. Duffy, Alfred Amambua-Ngwa, Kovana M. Loua, Eugene Laman, Davis C. Nwakanma, Bronwyn MacInnis, Harvey Aspeling-Jones, Lee Murray, Taane G. Clark, Dominic P. Kwiatkowski, David J. Conway
Journal: Molecular Biology and Evolution (2014)

Locally varying selection on pathogens may be due to differences in drug pressure, host immunity, transmission opportunities between hosts, or the intensity of between-genotype competition within hosts. Highly recombining populations of the human malaria parasite Plasmodium falciparum throughout West Africa are closely related, as gene flow is relatively unrestricted in this endemic region, but markedly varying ecology and transmission intensity should cause distinct local selective pressures. Genome-wide analysis of sequence variation was undertaken on a sample of 100 P. falciparum clinical isolates from a highly endemic region of the Republic of Guinea where transmission occurs for most of each year and compared with data from 52 clinical isolates from a previously sampled population from The Gambia, where there is relatively limited seasonal malaria transmission. Paired-end short-read sequences were mapped against the 3D7 P. falciparum reference genome sequence, and data on 136,144 single nucleotide polymorphisms (SNPs) were obtained. Within-population analyses identifying loci showing evidence of recent positive directional selection and balancing selection confirm that antimalarial drugs and host immunity have been major selective agents. Many of the signatures of recent directional selection reflected by standardized integrated haplotype scores were population specific, including differences at drug resistance loci due to historically different antimalarial use between the countries. In contrast, both populations showed a similar set of loci likely to be under balancing selection as indicated by very high Tajima's D values, including a significant overrepresentation of genes expressed at the merozoite stage that invades erythrocytes and several previously validated targets of acquired immunity. Between-population FST analysis identified exceptional differentiation of allele frequencies at a small number of loci, most markedly for five SNPs covering a 15-kb region within and flanking the gdv1 gene that regulates the early stages of gametocyte development, which is likely related to the extreme differences in mosquito vector abundance and seasonality that determine the transmission opportunities for the sexual stage of the parasite.
Chronic cough in patients with sleep-disordered breathing
Authors: K. K. Y. Chan, A. J. Ing, L. Laks, G. Cossa, P. Rogers, S. S. Birring
Journal: European Respiratory Journal (2010)

Chronic cough can be the sole presenting symptom for patients with obstructive sleep apnoea. We investigated the prevalence, severity and factors associated with chronic cough in patients with sleep-disordered breathing (SDB). We invited 108 consecutive patients who had been referred for evaluation of SDB to complete a comprehensive questionnaire on respiratory and sleep health, which included the Leicester Cough Questionnaire (cough specific quality of life; LCQ), Epworth Sleepiness Scale (ESS) and the Mayo Clinic gastro-oesophageal questionnaire. Chronic cough was defined as cough for a duration of >2 months. 33% of patients with SDB reported a chronic cough. Patients with a chronic cough had impaired cough related-quality of life affecting all health domains (mean+/-sem LCQ score 17.7+/-0.7; normal = 21). Patients with SDB and chronic cough were predominantly females (61% versus 17%; p<0.001) and reported more nocturnal heartburn (28% versus 5%; p = 0.03) and rhinitis (44% versus 14%; p = 0.02) compared to those without SDB. There were no significant differences in ESS, respiratory disturbance index, body mass index, or symptoms of breathlessness, wheeze, snoring, dry mouth and choking between those with cough and those without. Chronic cough is prevalent in patients with SDB and is associated with female sex, symptoms of nocturnal heartburn and rhinitis. Further studies are required to investigate the impact of continuous positive airway pressure therapy on cough associated with SDB to explore the mechanism of this association.
Measuring quality of life: Are quality of life measures patient centred?
Authors: A. J Carr
Journal: BMJ (2001)

This is the third in a series of five articles 

Quality of life measures are increasingly used to supplement objective clinical or biological measures of disease to assess the quality of service, the need for health care, the effectiveness of interventions, and in cost utility analyses. Their use reflects a growing appreciation of the importance of how patients feel and how satisfied they are with treatment in addition to the traditional focus on disease outcomes. In this respect, quality of life measures capture patients' perspectives of their disease and treatment, their perceived need for health care, and their preferences for treatment and outcomes. They are hailed as being patient centred. But the challenge in measuring quality of life lies in its uniqueness to individuals. Many of the existing measures of quality of life fail to take account of this by imposing standardised models of quality of life and preselected domains; they are thus measures of general health status rather than quality of life.

Questions arise as to whether such measures are truly patient centred and to what extent they actually represent the quality of life of individual patients or groups of patients. Do they simply describe a patient's health in terms of what health professionals or society believe constitutes quality of life for people who are ill, something that may include factors that have little relevance to or importance for patients?

This paper explores the extent to which standardised quality of life measures accurately quantify an individual patient's quality of life. It debates whether newer, individualised approaches, which allow patients to define their quality of life in relation to their goals and expectations, are more appropriate.

#### Summary points

Quality of life is an individual construct and measures should take account of this

Many widely used measures are not patient centred because of …
THE FINE STRUCTURE OF CLOTS FORMED FROM PURIFIED BOVINE FIBRINOGEN AND THROMBIN: A STUDY WITH THE ELECTRON MICROSCOPE
Authors: Clinton Van Zandt Hawn, Keith R. Porter
Journal: The Journal of Experimental Medicine (1947)

1. A technique has been described for the preparation of clots from purified fibrinogen and thrombin of bovine origin which are suitable for study with the electron microscope. Experiments have been carried out to compare the fine structure of clots prepared at various values of pH. 2. The clots are composed of meshworks of single and compound fibers. At pH 8.5 the unit fibers have a smaller average diameter than those formed at pH 7.6 or pH 6.3. The tendency for the lateral association of unit fibers into compound fibers is markedly increased as the pH is decreased. 3. A striking feature of all the clots studied is cross-striation of the unit fibers. The periodicity of these striae is quite constant throughout (approximately 250 A). There is a precise coincidence of the striations of the individual unit fibers where these are associated side by side to form compound fibers.
Pentraxin-3 Is a Novel Biomarker of Lung Carcinoma
Authors: Eleftherios P. Diamandis, Lee Goodglick, Chris Planque, Mark D. Thornquist
Journal: Clinical Cancer Research (2011)

Our objective was to validate the performance of three new candidate lung cancer biomarkers, pentraxin-3 (PTX3), human kallikrein 11 (KLK11), and progranulin.We analyzed by commercial ELISA, and with a blinded protocol, 422 samples from 203 patients with lung carcinoma, 180 individuals with high risk for lung cancer (heavy smokers), and 43 individuals with cancers other than lung. All samples were obtained from the Early Detection Research Network (Reference set A).We found that progranulin and KLK11 were not informative lung cancer biomarkers, with areas under the receiver operating characteristic curve (AUC; ROC), close to 0.50. However, PTX3 was an informative lung cancer biomarker, with considerable ability to separate lung cancer patients from high-risk controls. At 90% and 80% specificity, the sensitivities versus the high-risk control group were 37% and 48%, respectively. The discriminatory ability of PTX3 was about the same with all major subtypes and histotypes of lung cancer. The AUC of the ROC curves increased according to the disease stage, from 0.64 (stage I) to 0.72 (stage IV).PTX3, but not KLK11 or progranulin, is a new serum biomarker for lung carcinoma. Its diagnostic sensitivity and specificity is similar to other clinically used lung cancer biomarkers. More studies are needed to establish if PTX3 has clinical utility for lung cancer diagnosis and management.
Bronchiectasis-colonization and the factors that affect colonization
Authors: Sermin Börekçi, Deniz Demir, Çigdem Zuhur, Benan Müsellim
Journal: European Respiratory Journal (2013)

Aim: We aimed to evaluate the colonization and the factors affecting colonization in patients with bronchiectasis

Methods: Between 1996-2013 years,data of all patients who admitted to bronchiectasis clinic of Cerrahpasa medical school pulmonology department,and diagnosed with high resolution computed tomography or multislice computed tomography were evaluated retrospectively. Statical analysis was performed by using SPSS 15.0 programs.

Results: Colonization evaluated in 76 of 232 patients.60.5% of all cases were female, 39.5% were male.Mean age was 50±16. 41(53.9%) were nonsmoker,23(30.3%) were exsmokers, 19(11.8% )were active smokers.Mean duration of illness were 18±14 years.18(23.7%) cases were colonized.The main pathogen for colonization was P.aeruginosa(n=15,83.3%).Colonization with E.coli, H.influenzae or P.alcaligenes have been identified in each 1(1.35%) cases.Sputum, dyspnea, chest pain, and hemoptysis complaints were significantly higher in colonized patients(p  0.05).

Conclusion: Approximately one-quarter of patients with bronchiectasis are colonized. The colonization risk is high in patients with long diseases duration or in patients with cystic bronchiectasis.
A missed opportunity. Teaching medical students to help their patients successfully quit smoking
Authors: M. C. Fiore
Journal: JAMA (1994)

CIGARETTE smoking maintains its dubious distinction as the chief preventable cause of cancer in the United States, responsible for 30% of all cancers and resulting in 150 000 cancer deaths each year.<sup>1,2</sup>Despite widespread knowledge regarding the risks of tobacco, 26% of adults in the United States continue to smoke.<sup>3</sup>As a result, an epidemic of cancer continues in this country, blunting the dramatic improvements that have resulted from advances in other areas such as early detection and treatment. One important way to control the epidemic of tobacco-related cancers would be to improve the frequency and effectiveness of smoking interventions by physicians. While many programs have attempted to train practicing physicians,<sup>4</sup>no national program has focused on undergraduate medical education and the importance of reaching medical students during their primary medical training. In this article, we will review the findings of a National Cancer Institute (NCI) Expert
Thymus-leukemia (TL) antigens of the mouse. Analysis of TL mRNA and TL cDNA TL+ and TL- strains.
Authors: Y T Chen, Y Obata, E Stockert, L J Old
Journal: The Journal of Experimental Medicine (1985)

A thymus-leukemia (TL)-specific probe, pTL1, has been generated from a TL-coding gene of BALB/c mice. Multiple species of TL mRNA were detected in TL+ cells by Northern blot analysis with pTL1, and different Tla haplotypes could be distinguished on the basis of characteristic patterns of TL mRNA. No TL-related message was found in normal or leukemic TL- cells, including thymocytes from Tlab mice. However, TL mRNA could be detected in TL+ leukemias occurring in Tlab mice. A cDNA library has been made from ASL1 (a TL+ leukemia of A mice [Tlaa]), and pTL1+ clones have been sequenced. At least three structurally distinct TL genes are expressed in ASL1. Sequence comparison of TL genes from three Tla haplotypes indicates that TL genes are highly conserved (greater than 90% homology) and are more distantly related to H-2 genes. Several polyadenylation sites have been found in the 3' untranslated region of TL genes, and differential polyadenylation contributes to the size heterogeneity of TL transcripts. The predicted amino acid sequence of TL products indicates that TL and H-2 are similar in domain structure and disulfide bonds, but differ in glycosylation sites and in cytoplasmic domain sequences.
Contribution of energy systems during a Wingate power test.
Authors: J C Smith, D W Hill
Journal: British Journal of Sports Medicine (1991)

Six men performed a total of 23 modified Wingate power tests against 5.5 kp (53.9 N) resistance on a Monark 864 ergometer. Breath-by-breath VO2 was measured using a SensorMedics 4400 metabolic cart. Peak anaerobic power (highest 5 s; mean(s.e.m.)) was 819(16) W (11.1(0.6) W kg-1) and anaerobic capacity (work in 30 s; mean(s.e.m.)) was 18.2(0.2) kJ (248(11) J kg-1). Contributions of ATP-PC, glycolytic and aerobic systems each 5 s were estimated. ATP-PC power (mean(s.e.m.)) peaked at 750(14) W (10.2(0.6) W kg-1) in the first 5 s; glycolytic power (mean(s.e.m.] peaked at 497(11) W (6.8(0.7) W kg-1) between 10 and 15 s into the test; aerobic power (mean(s.e.m.)) peaked at 157(5) W (2.1(0.3) W kg-1) during the last 5 s of the test, and VO2 exceeded 90% VO2peak Over the entire 30 s, aerobic contribution was 16%, glycolytic contribution was 56%, and ATP-PC contribution was 28%. It is concluded that glycolytic power peaks within the first 15 s of high power exercise; also, aerobic metabolism responds quickly during 'anaerobic' exercise and makes a significant contribution to the work performed.
Alveolar lining fluid regulates mononuclear phagocyte 5-lipoxygenase metabolism
Authors: SM Phare, M Peters-Golden, MJ Coffey
Journal: European Respiratory Journal (1998)

The enzyme 5-lipoxygenase (5-LO) catalyses the synthesis of leukotrienes (LT), which are important in phagocytosis and killing of microorganisms. The alveolar macrophage (AM), the primary resident defender of the alveolar space, has a greater capacity for LT synthesis than its precursor, the peripheral blood monocyte (PBM). This study investigated whether the alveolar lining fluid (ALF) upregulates LT synthetic capacity in mononuclear phagocytes. Rat AM, peritoneal macrophages (PM) and ALF were obtained by lavage from pathogen-free animals. Human PBM were isolated from normal subjects. 5-LO metabolism and expression were measured with and without ALF. Rat ALF increased 5-LO metabolism (136.4+/-15.1% of control) in cultured PBM. This was associated with increased 5-LO activating protein (FLAP) (357+/-29.5 %), and 5-LO expression (188+/-31.3%). Culture of AM for 3 days resulted in a greater decrement in LTB4 synthesis (LTB4 15.4+/-6.9% of day 1) than in PM (54.7+/-8.3% of day 1), suggesting a greater dependence of AM 5-LO metabolism on ALF. 5-LO and FLAP expression decreased to a greater degree in AM than PM in culture. Furthermore, AM cultured with ALF maintained their LT synthetic capacity, FLAP and 5-LO expression compared with control cells cultured in medium alone. In conclusion, alveolar lining fluid increased 5-lipoxygenase metabolism in peripheral blood monocytes and maintained it in cultured alveolar macrophages, by a mechanism of increased 5-lipoxygenase and 5-lipoxygenase activating protein expression. This may boost host defence capabilities.
Central Nervous System Damage, Monocytes and Macrophages, and Neurological Disorders in AIDS
Authors: Kenneth C. Williams, William F. Hickey
Journal: Annual Review of Neuroscience (2002)

▪ Abstract This review focuses on the role of the extended macrophage/monocyte family in the central nervous system during HIV or SIV infection. The accumulated data, buttressed by recent experimental results, suggest that these cells play a central, pathogenic role in retroviral-associated CNS disease. While the immune system is able to combat the underlying retroviral infection, the accumulation and widespread activation of macrophages, microglia, and perivascular cells in the CNS are held in check. However, with the collapse of the immune system and the disappearance of the CD4 + T cell population, productive infection reemerges, especially in CNS macrophages. These cells, as well as noninfected macrophages, are stimulated to high levels of activation. When members of this cell group become highly activated, they elaborate a wide spectrum of deleterious substances into the neural parenchyma. In the final phases of HIV or SIV infection, this chronic, widespread, and dramatic level of macrophage/monocyte/microglial activation constitutes a self-sustaining state of macrophage dysregulation, which results in pathological alterations and the emergence of various neurological problems.
Cost-Effectiveness of CT Screening in the National Lung Screening Trial
Authors: William C. Black, Ilana F. Gareen, Samir S. Soneji, JoRean D. Sicks, Emmett B. Keeler, Denise R. Aberle, Arash Naeim, Timothy R. Church, Gerard A. Silvestri, Jeremy Gorelick, Constantine Gatsonis
Journal: New England Journal of Medicine (2014)

The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST. We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions. As compared with no screening, screening with low-dose CT cost an additional $1,631 per person (95% confidence interval [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI, 34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses. We estimated that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).
<i>PCOTH</i>, a Novel Gene Overexpressed in Prostate Cancers, Promotes Prostate Cancer Cell Growth through Phosphorylation of Oncoprotein TAF-Iβ/SET
Authors: Yoshio Anazawa, Hidewaki Nakagawa, Mutsuo Furihara, Shingo Ashida, Kenji Tamura, Hiroki Yoshioka, Taro Shuin, Tomoaki Fujioka, Toyomasa Katagiri, Yusuke Nakamura
Journal: Cancer Research (2005)

Through genome-wide cDNA microarray analysis coupled with microdissection of prostate cancer cells, we identified a novel gene, prostate collagen triple helix (PCOTH), showing overexpression in prostate cancer cells and its precursor cells, prostatic intraepithelial neoplasia (PIN). Immunohistochemical analysis using polyclonal anti-PCOTH antibody confirmed elevated expression of PCOTH, a 100-amino-acid protein containing collagen triple-helix repeats, in prostate cancer cells and PINs. Knocking down PCOTH expression by small interfering RNA (siRNA) resulted in drastic attenuation of prostate cancer cell growth, and concordantly, LNCaP derivative cells that were designed to constitutively express exogenous PCOTH showed higher growth rate than LNCaP cells transfected with mock vector, suggesting the growth-promoting effect of PCOTH on prostate cancer cell. To investigate the biological mechanisms of this growth-promoting effect, we applied two-dimensional differential gel electrophoresis (2D-DIGE) to analyze the phospho-protein fractions in LNCaP cells transfected with PCOTH. We found that the phosphorylation level of oncoprotein TAF-Ibeta/SET was significantly elevated in LNCaP cells transfected with PCOTH than control LNCaP cells, and these findings were confirmed by Western blotting and in-gel kinase assay. Furthermore, knockdown of endogenous TAF-Ibeta expression by siRNA also attenuated viability of prostate cancer cells as well. These findings suggest that PCOTH is involved in growth and survival of prostate cancer cells thorough, in parts, the TAF-Ibeta pathway, and that this molecule should be a promising target for development of new therapeutic strategies for prostate cancers.