tbuckley/cabot-search huggingface dataset:
Integrin dependent migration of lung cancer cells to extracellular matrix components
Authors: CG Bredin, KG Sundqvist, D Hauzenberger, J Klominek
Journal: European Respiratory Journal (1998)

Since tumour progression is dependent on the ability of malignant cells to interact with the extracellular matrix (ECM), we have investigated the significance of beta1 and beta3 integrins for migration of lung cancer cells to components of the ECM. In an in vitro hapto- and chemotactic assay system, five cell lines representing the major types of lung cancer were examined: adenocarcinoma (WART); squamous cell carcinoma (U-1752); small cell lung cancer (SCLC) (U-1906, 054 A) and large cell lung cancer (LCLC) (U-1810). Flow cytometric analyses were performed to characterize their integrin expression. U-1906, 054 A, WART and U-1752 all expressed beta1 integrins whereas U-1810 did not. However, U-1810 and U-1752 expressed beta3 integrins. All cell lines except U-1810 and U-1752 showed hapto- and chemotactic motility to fibronectin, laminin and type IV collagen and this motility was beta1 integrin-dependent except in the case of U-1810. However, the hapto- and chemotactic responses differed markedly between the separate cell lines and there was no distinct pattern to separate non-small cell lung cancer (NSCLC) from SCLC. No or very little migration was seen in control experiments with bovine serum albumin (BSA) or serum-free medium alone, indicating that the migration of the lung cancer cells require adhesion molecules, soluble or substratum bound. We have found the involvement of beta1 integrins in lung cancer cell migration in vitro towards fibronectin, laminin and type IV collagen except in the case of U-1810. The U-1810 cell line clearly differed from the rest of the cell lines by lacking expression of beta1 integrins.
Natural killer cell regulation of age-related and type-specific variations in antibody responses to pneumococcal polysaccharides.
Authors: M Khater, J Macai, C Genyea, J Kaplan
Journal: The Journal of Experimental Medicine (1986)

Pretreatment of mice with anti-asialo GM1, which has been shown to deplete NK cytolytic activity without affecting cytotoxic T cells or macrophages, increased the weak anti-PPS 6 responses of adult mice to levels similar to that of their anti-PPS 3 responses, and increased the weak-to-absent anti-PPS 3 and anti-PPS 6 responses of weanling mice to the same levels as achieved by adult mice. By contrast, pretreatment with poly(IC), which augments NK activity, resulted in a 14-fold reduction in the anti-PPS 3 responses of adult mice. The enhancement of anti-PPS responses in mice treated with anti-asialo GM1 was due to inactivation or depletion of NK cells, and not T suppressor cells, since this enhancement occurred in athymic nude mice as well as in euthymic mice. In addition, strains of mice with low or absent endogenous NK activity were found to have considerably stronger anti-PPS responses than strains of mice with normal NK activity. NK depletion enhanced anti-PPS 6 IgM but not IgG response, and resulted in a true increase in antibody production rather than an alteration in the time course of the response. These findings indicate that NK cells physiologically downregulate anti-PPS responses, and that age-dependent and type-specific variations in these responses are primarily determined by NK regulatory effects.
Is Neighborhood Green Space Associated With a Lower Risk of Type 2 Diabetes? Evidence From 267,072 Australians
Authors: Thomas Astell-Burt, Xiaoqi Feng, Gregory S. Kolt
Journal: Diabetes Care (2013)

OBJECTIVE Lifestyle interventions for type 2 diabetes mellitus (T2DM) are best positioned for success if participants live in supportive neighborhood environments. Deprived neighborhoods increase T2DM risk. Parks and other "green spaces" promote active lifestyles and therefore may reduce T2DM risk. We investigated association between neighborhood green space and the risk of T2DM in a large group of adult Australians. RESEARCH DESIGN AND METHODS Multilevel logit regression was used to fit associations between medically diagnosed T2DM and green space exposure among 267,072 participants in the 45 and Up Study. Green space data were obtained from the Australian Bureau of Statistics, and exposure was calculated using a 1-km buffer from a participant's place of residence. Odds ratios (ORs) were controlled for measures of demographic, cultural, health, diet, active lifestyles, socioeconomic status, and neighborhood circumstances. RESULTS The rate of T2DM was 9.1% among participants in neighborhoods with 0-20% green space, but this rate dropped to approximately 8% for participants with over 40% green space within their residential neighborhoods. The risk of T2DM was significantly lower in greener neighborhoods, controlling for demographic and cultural factors, especially among participants residing in neighborhoods with 41-60% green space land use (OR 0.87; 95% CI 0.83-0.92). This association was consistent after controlling for other explanatory variables and did not vary according to neighborhood circumstances. CONCLUSIONS People in greener surroundings have a lower risk of T2DM. Planning, promoting, and maintaining local green spaces is important in multisector initiatives for addressing the T2DM epidemic.
Double-blind, placebo-controlled study of oral calcitriol for the treatment of localized and systemic scleroderma
Authors: M.M. Hulshof, J.N.Bouwes Bavinck, W. Bergman, A.A.M. Masclee, L. Heickendorff, F.C. Breedveld, B.A.C. Dijkmans
Journal: Journal of the American Academy of Dermatology (2000)
Idiopathic Nonspecific Interstitial Pneumonia
Authors: William D. Travis, Gary Hunninghake, Talmadge E. King, David A. Lynch, Thomas V. Colby, Jeffrey R. Galvin, Kevin K. Brown, Man Pyo Chung, Jean-François Cordier, Roland M. du Bois, Kevin R. Flaherty, Teri J. Franks, David M. Hansell, Thomas E. Hartman, Ella A. Kazerooni, Dong Soon Kim, Masanori Kitaichi, Takashi Koyama, Fernando J. Martinez, Sonoko Nagai, David E. Midthun, Nestor L. Müller, Andrew G. Nicholson, Ganesh Raghu, Moisés Selman, Athol Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The 2002 American Thoracic Society/European Respiratory Society classification of idiopathic interstitial pneumonias identified nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis. Concern was expressed that NSIP was a "wastebasket" category, difficult to distinguish from other idiopathic interstitial pneumonias.The following questions were addressed: (1) Is idiopathic NSIP a distinct entity? 2) If so, what are its clinical, radiologic and pathologic characteristics? (3) What is the role of radiology and pathology in establishing the diagnosis? (4) To make a diagnosis of idiopathic NSIP, what other disorders need to be excluded and how should this be done?Investigators who had previously reported cases of idiopathic NSIP were invited to submit cases for review (n = 305). After initial review, cases with complete clinical, radiologic, and pathologic information (n = 193) were reviewed in a series of workshops.Sixty-seven cases were identified as NSIP. Mean age was 52 years, 67% were women, 69% were never-smokers, and 46% were from Asian countries. The most common symptoms were dyspnea (96%) and cough (87%); 69% had restriction. By high-resolution computed tomography, the lower lung zones were predominantly involved in 92% of cases; 46% had a peripheral distribution; 47% were diffuse. Most showed a reticular pattern (87%) with traction bronchiectasis (82%) and volume loss (77%). Lung biopsies showed uniform thickening of alveolar walls with a spectrum of cellular to fibrosing patterns. Five-year survival was 82.3%.Idiopathic NSIP is a distinct clinical entity that occurs mostly in middle-aged women who are never-smokers. The prognosis of NSIP is very good.
L2L: a simple tool for discovering the hidden significance in microarray expression data.
Authors: John C Newman, Alan M Weiner
Journal: Genome biology (2005)

L2L is a database consisting of lists of differentially expressed genes compiled from published mammalian microarray studies, along with an easy-to-use application for mining the database with the user's own microarray data. As illustrated by re-analysis of a recent study of diabetic nephropathy, L2L identifies novel biological patterns in microarray data, providing insights into the underlying nature of biological processes and disease. L2L is available online at the authors' website [http://depts.washington.edu/l2l/].
Integrative analysis of DNA copy number and gene expression in metastatic oral squamous cell carcinoma identifies genes associated with poor survival
Authors: Chang Xu, Yan Liu, Pei Wang, Wenhong Fan, Tessa C Rue, Melissa P Upton, John R Houck, Pawadee Lohavanichbutr, David R Doody, Neal D Futran, Lue Ping Zhao, Stephen M Schwartz, Chu Chen, Eduardo Méndez
Journal: Molecular Cancer (2010)

Abstract Background Lymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC. Results We performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate &lt; 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with p = 0.044 or 0.011, respectively). Conclusions Genes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.
Drug Administration Schedules
Authors: ALBERTO DIMASCIO, RICHARD I. SHADER
Journal: American Journal of Psychiatry (1969)

Common current practice is to prescribe psychotropic drugs so that a specified daily amount is administered in equally divided doses on a three to six times a day schedule. The authors contend that this procedure rests on no valid scientific basis. They cite a number of pharmacologic facts to bolster this conclusion and review the effects and effectiveness of various schedules of drug administration. They conclude that revisions can be made in the present methods of drug administration that result in great pragmatic benefit without loss of therapeutic effect.
Dual gene therapy with SERCA1 and Kir2.1 abbreviates excitation without suppressing contractility
Authors: Irene L. Ennis, Ronald A. Li, Anne M. Murphy, Eduardo Marbán, H. Bradley Nuss
Journal: Journal of Clinical Investigation (2002)

Heart failure is characterized by depressed contractility and delayed repolarization. The latter feature predisposes the failing heart to ventricular arrhythmias and represents a logical target for gene therapy. Unfortunately, unopposed correction of the delay in repolarization will decrease the time available for calcium cycling during each heartbeat, potentially aggravating the depression of contractility. Here we describe the development and application of a novel gene therapy strategy designed to abbreviate excitation without depressing contraction. The calcium ATPase SERCA1 was coexpressed with the potassium channel Kir2.1 in guinea pig hearts. Myocytes from the hearts had bigger calcium transients and shorter action potentials. In vivo, repolarization was abbreviated, but contractile function remained unimpaired. Dual gene therapy of the sort described here can be generalized to exploit opposing or synergistic therapeutic principles to achieve a tailored phenotype.
Low-dose corticosteroid use and mortality in severe community-acquired pneumonia patients
Authors: Takashi Tagami, Hiroki Matsui, Hiromasa Horiguchi, Kiyohide Fushimi, Hideo Yasunaga
Journal: European Respiratory Journal (2014)

The relationship between low-dose corticosteroid use and mortality in patients with severe community-acquired pneumonia (CAP) remains unclear. 6925 patients with severe CAP who received mechanical ventilation with or without shock (defined as use of catecholamines) at 983 hospitals were identified using a Japanese nationwide administrative database. The main outcome measure was 28-day mortality. 2524 patients with severe CAP who received catecholamines were divided into corticosteroid (n=631) and control (n=1893) groups. The 28-day mortality was significantly different between corticosteroid and control groups (unmatched: 24.6% versus 36.3%, p&lt;0.001; propensity score-matched: 25.3% versus 32.6%, p=0.01; inverse probability-weighted: 27.5% versus 34.2%, p&lt;0.001). 4401 patients with severe CAP who did not receive catecholamines were also divided into corticosteroid (n=1112) and control (n=3289) groups. The 28-day mortality was not significantly different between corticosteroid and control groups in propensity score-matched analyses (unmatched: 16.0% versus 19.4%, p=0.01; propensity score-matched: 17.7% versus 15.6%, p=0.22; inverse probability-weighted: 18.8% versus 18.2%, p=0.44). Low-dose corticosteroid use may be associated with reduced 28-day mortality in patients with septic shock complicating CAP.
Neoadjuvant Therapy as a Platform for Drug Development and Approval in Breast Cancer
Authors: Aditya Bardia, José Baselga
Journal: Clinical Cancer Research (2013)

Abstract The traditional drug development process in breast cancer based on large phase III studies has serious limitations and needs a major overhaul. Searching for new approaches, the testing of novel agents in the preoperative (neoadjuvant) setting approach offers a potentially rapid and efficient strategy for drug development utilizing pathologic complete response (path CR), a surrogate marker for survival, as the primary endpoint. In addition, neoadjuvant studies allow the assessment of drug effects on the target (pharmacodynamic response) and the development of predictive biomarkers of response. Molecular profiling of the residual tumor in the surgical specimen may also provide insights into actionable mechanisms of resistance. Recognizing the potential of neoadjuvant trials for drug development, the U.S. Food and Drug Administration (FDA) recently announced consideration of neoadjuvant trials for accelerated drug approval in early breast cancer, particularly for tumors with high risk of recurrence and unfavorable prognosis, and provided accelerated approval to neoadjuvant pertuzumab in September 2013. The FDA has emphasized that while improvement in path CR could be utilized for “accelerated” approval, improvement in survival will still need to be demonstrated for “regular” approval. Key considerations in conduct of such neoadjuvant drug development trials include (i) study design such as utilization of biomarker stratified design to evaluate a biomarker that could enrich response, (ii) definition of path CR, (iii) distribution of factors that influence path CR between the treatment arms, (iv) prespecified plan for follow-up to obtain data on survival, and (v) safety as it involves a patient population with curable disease. In the years to come, we anticipate an increase in the number of neoadjuvant trials testing novel therapies that hopefully will open a new path in bringing efficacious new therapies to patients with breast cancer. Clin Cancer Res; 19(23); 6360–70. ©2013 AACR.
Nonallelic Gene Conversion Is Not GC-Biased in Drosophila or Primates
Authors: Raquel Assis, Alexey S. Kondrashov
Journal: Molecular Biology and Evolution (2011)

Gene conversion is the unidirectional transfer of genetic information between allelic (orthologous) or nonallelic (paralogous) DNA segments. Recently, there has been much interest in understanding how gene conversion shapes the nucleotide composition of the genomic landscape. A widely held hypothesis is that gene conversion is universally GC-biased. However, direct experimental evidence of this hypothesis is limited to a single study of meiotic crossovers in yeast. Although there have been a number of indirect studies of gene conversion, evidence of GC-biased replacements gathered from such studies can also be attributed to positive selection, which has the same evolutionary dynamics as biased gene conversion. Here, we apply a direct phylogenetic approach to examine nucleotide replacements produced by nonallelic gene conversion in Drosophila and primate genomes. We find no evidence for GC-biased gene conversion in either lineage, suggesting that previously observed GC biases may be due to positive selection rather than to biased gene conversion.
The Gtpase Rho Controls a P53-Dependent Survival Checkpoint during Thymopoiesis
Authors: Patrick S. Costello, Steve C. Cleverley, Ricciarda Galandrini, Stefan W. Henning, Doreen A. Cantrell
Journal: The Journal of Experimental Medicine (2000)

During the early stages of thymopoiesis, cell survival is controlled by cytokines that regulate the expression of antiapoptotic proteins such as Bcl-2. At the pre-T cell stage, a critical checkpoint for β chain selection is monitored by the tumor suppressor p53: pre-T cells can survive and differentiate when p53 is removed genetically or when its proapoptotic function is inactivated physiologically as a consequence of signaling through the pre-T cell receptor complex. Previous work has shown that the guanine nucleotide binding protein Rho controls cell survival in T cell progenitors. Here we define the survival pathways controlled by Rho in pre-T cells and show that this GTPase is a pivotal regulator of the p53-mediated checkpoint operating at the time of β selection: loss of Rho function results in apoptosis in pre-T cells, but this cell death is prevented by loss of p53. The prevention of cell death by loss of p53 restored numbers of early T cell progenitors but did not fully restore thymic cellularity. Further analysis revealed that loss of Rho function caused survival defects in CD4/8 double-positive thymocytes that is independent of p53 but can be prevented by ectopic expression of Bcl-2. These studies highlight that the GTPase Rho is a crucial component of survival signaling pathways in at least two different thymocyte subpopulations: Rho controls the p53 survival checkpoint in pre-T cells and is also crucial for a p53 independent survival signaling pathway in CD4/8 double positives.
Vitamin E Attenuates Oxidative Stress Induced by Intravenous Iron in Patients on Hemodialysis
Authors: JOHANNES M. ROOB, GHOLAMALI KHOSCHSORUR, ANDREAS TIRAN, JÖRG H. HORINA, HERWIG HOLZER, BRIGITTE M. WINKLHOFER-ROOB
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Intravenous iron application to anemic patients on hemodialysis leads to an “oversaturation” of transferrin. As a result, non-transferrin-bound, redox-active iron might induce lipid peroxidation. To test the hypothesis that vitamin E attenuates lipid peroxidation in patients receiving 100 mg of iron(II) hydroxide sucrose complex intravenously during a hemodialysis session, 22 patients were investigated in a randomized cross-over design, either with or without a single oral dose of 1200 IU of all-rac-α-tocopheryl acetate taken 6 h before the hemodialysis session. Blood was drawn before and 30, 60, 90, 135, and 180 min after the start of the iron infusion, and areas under the curve (AUC 0-180 min ) of ratios of plasma malondialdehyde (MDA) to cholesterol and plasma total peroxides to cholesterol (two markers of lipid peroxidation) were determined as the outcome variables. At baseline of the session without vitamin E supplementation, plasma α-tocopherol concentrations (27.6 ± 1.8 μmol/L) and ratios of α-tocopherol to cholesterol (5.88 ± 1.09 mmol/mol) were normal, plasma MDA concentrations were above normal (1.20 ± 0.28 μmol/L), and bleomycin-detectable iron (BDI), indicating the presence of redox-active iron, was not detectable. Upon iron infusion, BDI and MDA concentrations increased significantly ( P &lt; 0.001). BDI concentrations explained the increase over baseline in MDA concentrations (MDA = 1.29 + 0.075 × BDI). Vitamin E supplementation, leading to a 68% increase in plasma α-tocopherol concentrations, significantly reduced the AUC 0-180 min of MDA to cholesterol ( P = 0.004) and peroxides to cholesterol ( P = 0.002). These data demonstrate that a single oral dose of vitamin E attenuates lipid peroxidation in patients on hemodialysis receiving intravenous iron. Given that intravenous iron is applied repeatedly to patients on hemodialysis, this therapeutic approach may protect against oxidative stress-related degenerative disease in the long term.
Platinum-based chemotherapy in metastatic triple-negative breast cancer: the Institut Curie experience
Authors: L. Staudacher, P.H. Cottu, V. Diéras, A. Vincent-Salomon, M.N. Guilhaume, L. Escalup, T. Dorval, P. Beuzeboc, L. Mignot, J.Y. Pierga
Journal: Annals of Oncology (2010)
Home based neuromuscular electrical stimulation as a new rehabilitative strategy for severely disabled patients with chronic obstructive pulmonary disease (COPD)
Authors: J A Neder
Journal: Thorax (2002)

Background: Passive training of specific locomotor muscle groups by means of neuromuscular electrical stimulation (NMES) might be better tolerated than whole body exercise in patients with severe chronic obstructive pulmonary disease (COPD). It was hypothesised that this novel strategy would be particularly effective in improving functional impairment and the consequent disability which characterises patients with end stage COPD. Methods: Fifteen patients with advanced COPD (nine men) were randomly assigned to either a home based 6 week quadriceps femoris NMES training programme (group 1, n=9, FEV<sub>1</sub>=38.0 (9.6)% of predicted) or a 6 week control period before receiving NMES (group 2, n=6, FEV<sub>1</sub>=39.5 (13.3)% of predicted). Knee extensor strength and endurance, whole body exercise capacity, and health related quality of life (Chronic Respiratory Disease Questionnaire, CRDQ) were assessed. Results: All patients were able to complete the NMES training programme successfully, even in the presence of exacerbations (n=4). Training was associated with significant improvements in muscle function, maximal and endurance exercise tolerance, and the dyspnoea domain of the CRDQ (p&lt;0.05). Improvements in muscle performance and exercise capacity after NMES correlated well with a reduction in perception of leg effort corrected for exercise intensity (p&lt;0.01). Conclusions: For severely disabled COPD patients with incapacitating dyspnoea, short term electrical stimulation of selected lower limb muscles involved in ambulation can improve muscle strength and endurance, whole body exercise tolerance, and breathlessness during activities of daily living.