tbuckley/cabot-search huggingface dataset:
Shuffling of cis-regulatory elements is a pervasive feature of the vertebrate lineage.
Authors: Remo Sanges, Eva Kalmar, Pamela Claudiani, Maria D'Amato, Ferenc Muller, Elia Stupka
Journal: Genome biology (2006)

Abstract Background All vertebrates share a remarkable degree of similarity in their development as well as in the basic functions of their cells. Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development. Results We used a unique combination of tools to obtain regional global-local alignments of orthologous loci. This approach takes into account shuffling of regulatory regions that are likely to occur over evolutionary distances greater than those separating mammalian genomes. This approach revealed one order of magnitude more vertebrate conserved elements than was previously reported in over 2,000 genes, including a high number of genes found in the membrane and extracellular regions. Our analysis revealed that 72% of the elements identified have undergone shuffling. We tested the ability of the elements identified to enhance transcription in zebrafish embryos and compared their activity with a set of control fragments. We found that more than 80% of the elements tested were able to enhance transcription significantly, prevalently in a tissue-restricted manner corresponding to the expression domain of the neighboring gene. Conclusion Our work elucidates the importance of shuffling in the detection of cis -regulatory elements. It also elucidates how similarities across the vertebrate lineage, which go well beyond development, can be explained not only within the realm of coding genes but also in that of the sequences that ultimately govern their expression.
Osteogenic sarcoma with clinically detectable metastasis at initial presentation.
Authors: P A Meyers, G Heller, J H Healey, A Huvos, A Applewhite, M Sun, M LaQuaglia
Journal: Journal of Clinical Oncology (1993)

Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease.From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease.Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival.OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients.
Safety of psychotropic drugs in pregnancy
Authors: H. Khalifeh, C. Dolman, L. M. Howard
Journal: BMJ (2015)

Reassuring findings on antidepressants and antipsychotics from the largest studies to date

Mental illness in pregnancy is common—around 10% of women experience a major depressive illness or anxiety disorder,1 and an increasing number of women with psychotic disorders are able to conceive owing to the decreased use of antipsychotics with prolactin raising properties.2 Women who have severe mental illness in the perinatal period are at risk of considerable psychological morbidity, including suicide,2 but they often discontinue psychotropics,3 largely because of concerns about safety.4 Evidence on the risks of drugs from observational data is limited and contradictory, with important methodological limitations due to bias, confounding, and small sample sizes.5 In two linked papers in this issue, Furu and colleagues (doi:10.1136/bmj.h17986 and Vigod and colleagues (doi:10.1136/bmj.h2298)7 tackle some of these limitations by using novel methods to reduce confounding in large linked datasets, and thus provide a valuable addition to the evidence base on the safety of psychotropic drugs in pregnancy.

Furu and colleagues used national data from the five Nordic countries to examine the association between maternal use of selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in the first trimester and birth defects among 2.3 million live singletons, including 36 772 (1.6%) exposed infants. To account for familial or unmeasured …
The Adrenergic Control of Lower Esophageal Sphincter Function
Authors: Anthony J. DiMarino, Sidney Cohen
Journal: Journal of Clinical Investigation (1973)

To evaluate the adrenergic regulation of lower esophageal sphincter (LES) function, LES pressure, LES relaxation during swallowing, and blood pressure were measured in the anesthetized opossum, Didelphis virginiana, during intravenous administration of alpha and beta adrenergic agonists and antagonists. Studies were done in controls and animals adrenergically denervated with 6-hydroxydopamine. Alpha adrenergic agonists (norepinephrine, phenylephrine) increased LES pressure and blood pressure, whereas a beta adrenergic agonist (isoproterenol) decreased both pressures. Alpha adrenergic antagonism (phentolamine) reduced basal LES pressure by 38.3±3.8% (mean ±SEM) (P < 0.001). Beta adrenergic antagonism (propranolol) had no significant effect on either basal LES pressure or percent of LES relaxation with swallowing. After adrenergic denervation with 6-hydroxydopamine, basal LES pressure was reduced by 22.5±5.3% (P < 0.025) but LES relaxation during swallowing was unaltered. In denervated animals, both LES pressure and blood pressure dose response curves showed characteristics of denervation supersensitivity to alpha but not to beta adrenergic agonists. These studies suggest: (a) a significant portion of basal LES pressure is dependent upon alpha adrenergic stimulation; (b) LES relaxation during swallowing is not an adrenergically mediated response; (c) the LES pressure response to alpha adrenergic agonists after 6-hydroxydopamine may serve as a model of denervation supersensitivity in the gastrointestinal tract.
Early cancer therapy response assessment by quantitative F-18 FDG PET/CT
Authors: James M. Mountz, Charles Laymon, Erin Deeb, Yin Jie Chen
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Reliable noninvasive quantitative methods for assessing early response to chemotherapy are vital for development of more personalized cancer therapy management, by allowing earlier decisions regarding therapy changes. The CT RECIST method is widely used; however, CT does not provide information on the physiologic properties of the tumor. In this study, F-18 FDG (FDG) PET is compared to CT in predicting response to chemotherapy using changes in imaging biomarkers of tumor metabolism and size early after initiation of therapy compared to baseline (BL) and follow-up. Materials and Methods: Nine patients with malignant cancer (lung, colorectal, or lymphoma) entered this early therapy response study. All patients received a BL scan before the initiation of chemotherapy, an early therapy assessment (ETA) scan between 2 to 7 weeks after initiation of therapy, and a study end point (FTA) scan between 3 to 9 months. The average length of time between ETA and FTA scans was 4 months. All PET/CT scans were performed on GE ST PET/CT scanner, approximately 60 min after patients received IV injection of approximately 15 mCi of F-18 FDG. All PET/CT images were registered and analyzed on MIMvista workstation to calculate FDG SUV values and CT RECIST measurements. By comparing BL and FTA scans, patients were classified as responders or non-responders based on RECIST. To compare FDG PET and CT data, the largest tumor was identified on CT at BL and its area and SUV were measured at ETA and FTA in each patient. Results: At FTA, responders had an average (FTA CT area)/(BL CT area) of 0.40 and average (FTA SUV)/(BL SUV) of 0.25. For non-responders, these values were 1.55 and 1.27 respectively. At ETA, for responders, (ETA CT area)/(BL CT area) averaged 0.65 and (ETA SUV)/(BL SUV) averaged 0.26. For non-responders, these values were 1.19 and 1.15 respectively. Conclusion: FDG uptake reduction at ETA compared to BL can be used to distinguish responders from non-responders, classified based upon RECIST at FTA. This early change in FDG uptake is more sensitive than early CT changes in predicting response to chemotherapy at FTA. Research Support: This research was supported in part by grant U01 CA140230 from the National Cancer Institute to Dr. Mountz.
The relationship between exhaled nitric oxide and compliance/adherence in patients with bronchial asthma using inhaled corticosteroids
Authors: Yuko Amimoto, Naohiko Taba, Yoko Murakami, Chikako Motomura, Hiroshi Odajima
Journal: European Respiratory Journal (2012)

Background: The measurement of FENO is the important index to evaluate the control of the patients with bronchial asthma using inhaled corticosteroids (ICS). When FENO in the patients using ICS is high, we often try to increase the dose of ICS. However, it is necessary to take compliance/adherence of the patients into consideration before that.  Objectives: The aim of this study was to examine whether the measurement of FENO is useful as the index of compliance/adherence to asthma treatment by ICS.  Methods: One hundred forty-seven subjects (4 to 23 years of age; 82 male, 65 female) with bronchial asthma using ICS were recruited from the outpatient division at the Department of Pediatrics at Fukuoka National Hospital between January-August in 2011. We measured their FENO and asked them to complete a questionnaire regarding the use of ICS. We asked them how often they inhaled ICS for a month, and classified them into five groups categorized as the grade of compliance. Additionally, we made a questionnaire about adherence. The patients answered that they inhaled ICS by themselves were defined as good adherence group, and otherwise as poor adherence group. We compared FENO in 5 groups categorized as the grade of compliance. Likewise, we also compared FENO in good and poor adherence groups.  Results: FENO in the patients of good compliance groups were significantly lower than that of poor compliance groups (p  Conclusions: It was indicated that the measurement of FENO could be useful as the index of compliance to asthma treatment by ICS.
Relationship between exercise capacity and the severity of emphysema as determined by high resolution CT
Authors: K Wakayama, N Kurihara, S Fujimoto, M Hata, T Takeda
Journal: European Respiratory Journal (1993)

We investigated the relationship between exercise capacity or exercise-induced hypoxaemia and the severity of pulmonary emphysema in 20 patients with pulmonary emphysema. The patients underwent pulmonary function tests, high resolution computed tomography and incremental treadmill exercise testing. Computed tomography scans were obtained at four levels in the lungs, and emphysema scores were determined by the visual assessment of low attenuation areas as a measure of the severity of parenchymal destruction. The emphysema score correlated significantly with diffusing capacity (r = -0.69) in the pulmonary function tests. Among the exercise test parameters, the emphysema score correlated significantly with the total distance walked (r = -0.74), with maximal oxygen consumption (VO2max) (r = -0.77), with arterial oxygen tension (PaO2) at rest (r = -0.50) and at the maximum workload (r = -0.58), and with the decrement of arterial oxygen tension per litre of oxygen consumed (r = -0.64). These results suggest that exercise capacity and exercise-induced hypoxaemia are related to the extent of destruction of lung parenchyma in patients with pulmonary emphysema.
Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain
Authors: F. Gutiérrez, M. Masiá, J.C. Rodríguez, C. Mirete, B. Soldán, S. Padilla, I. Hernández, F. De Ory, G. Royo, A.M. Hidalgo
Journal: Clinical Microbiology and Infection (2005)
Evaluation of cell spectrum in induced sputum of young cigarette smokers
Authors: Agnese Kislina, Gunta Strazda, Liga Balode, Zane Sinkevica, Darja Isajeva, Sergejs Isajevs, Normunds Jurka, Immanuels Taivans, Valentina Gordjusina, Viesturs Silins
Journal: European Respiratory Journal (2012)

It is of great importance to be able to diagnose early inflammatory changes that can lead to COPD in airways of young cigarette smokers.   Aim : The aim of this study was to analyze the cell spectrum of induced sputum in young cigarette smokers, with emphasis on T-regulatory cells.   Method : 20 healthy non-allergic smokers (Mean Age - 22±0.84; regular usage - 2.60±1.18 pack-years), and 20 non-smokers gave informed consent to participate in the study. Lung function measurements, sputum induction (IS) and sputum cell analyses were preformed.   Results : Demographic data for both study groups did not differ significantly. Both non-smokers and smokers had normal lung function indices. Induced sputum of smokers contained higher (p = 0.021) absolute amount of neutrophils [29.70 (20.96 – 42.09), cellsx10 4 /mL], compared with non-smokers [16.51 (11.65 – 23.39) cellsx10 4 / mL]. FOXP3-positive T reg cells in sputum of young smokers showed a trend towards statistically significant increase [11.10 (7.75 – 15.88) cellsx10 4 / mL], compared with non-smokers [6.79 (4.75 – 9.72) cellsx10 4 / mL, p = 0.057]. Regression analysis showed significant dependency of FOXP3-positive T reg cells (r 2  = 0.103; p = 0.044), neutrophils (r 2  = 0.179; p = 0.007) and macrophages of induced sputum (r 2  = 0.118; p = 0.030) from the number of smoked pack–years.   Conclusion : This study demonstrates that young smokers have early inflammatory changes in their airways, which not only initiate non-specific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T reg lymphocytes. The lymphocyte response is probably adaptive.
Predictive value of serum III procollagen for diagnosis of pulmonary involvement in patients with scleroderma
Authors: E Diot, P Diot, C Valat, E Boissinot, E Asquier, E Lemarie, JL Guilmot
Journal: European Respiratory Journal (1995)

High resolution computed tomography (HRCT) was recently demonstrated to be as good as open lung biopsy for the diagnosis of pulmonary involvement in patients with scleroderma. Nevertheless, in view of its price and related irradiation, HRCT cannot be recommended as a screening test. Serum III procollagen (sPIIINP) is an aminopropeptide of type III collagen, which is released during conversion into collagen by specific proteases. Increased levels of sPIIINP have been observed in patients with scleroderma. The aim of the present study was to assess the relationship between sPIIINP measurement and pulmonary involvement defined according to HRCT and pulmonary function tests (PFT) with single-breath carbon monoxide transfer capacity (TL,CO) in 28 patients suffering from scleroderma. Patients were divided into two groups for analysis, Group A comprising 16 patients without pulmonary scleroderma and Group B comprising 12 patients with pulmonary scleroderma. All patients had stable cutaneous disease and normal renal and hepatic function. The level of sPIIINP was determined by radioimmunoassay (RIA-gnost P-III-P, Prod. Nr. ODMT; Behring, Marburg, Germany). Mean +/- SD sPIIINP level in Group A was 0.85 +/- 0.21 U.mL-1. Individual values ranged 0.6-1.3 U.mL-1. Mean +/- SD sPIIINP value was 1.30 +/- 0.40 U.mL-1 in Group B and individual values ranged 0.7-1.9 U.mL-1. The difference in mean sPIIINP level between Group A and Group B was significant. Using a cut-off at 1.1 U.mL-1, sensitivity of sPIIINP was 0.66, specificity 0.94, positive predictive value 0.89, negative predictive value 0.79, false positive rate 0.06, and false negative rate 0.33. The value of sPIIINP correlated with HRCT score but not with PFT. This study confirms the relationship between sPIIINP and scleroderma with interstitial lung disease. We suggest that sPIIINP could be measured in patients with scleroderma to screen those patients requiring HRCT. Further studies are necessary to determine the value of sPIIINP in terms of prognosis and follow-up of patients under treatment.
Unique Proliferation-Associated Marker Expressed on Activated and Transformed Human Cells Defined by Monoclonal Antibody&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Devendra P. Dubey, Donald E. Staunton, Amritlal C. Parekh, Gerald A. Schwarting, Demetri Antoniou, Herbert Lazarus, Edmond J. Yunis
Journal: JNCI Journal of the National Cancer Institute (1987)

The expression, tissue distribution, and preliminary characterization of a cell surface molecule, apparently a glycolipid, recognized by a monoclonal antibody, anti-PAA, were described. This antibody (anti-PAA) was produced by the fusion of myeloma cells NS-1 with spleen cells from a BALB/c mouse, which were sensitized with activated human T-cells generated by allogeneic stimulation in mixed-lymphocyte culture (MLC). Resting human peripheral blood T-cells, B-cells, and monocytes demonstrated weak anti-PAA binding. Binding of proliferating T-cells (phytohemagglutinin- and MLC-activated T-cells) and thymocytes to anti-PAA was two to six times greater than that of resting T-cells. A fifteenfold-increased binding was observed with acute lymphocytic leukemia T-cell lines. Epstein-Barr virus-transformed B-cell lines bound anti-PAA up to sixteenfold greater than resting B-cells. Tumor cell lines of various nonlymphoid origins demonstrated marked reactivity with this antibody. Both benign and malignant cells in hyperplastic tissues, of various origins, bound anti-PAA, whereas their normal, nonproliferating counterparts did not. Normal proliferating cells in these tissues, including cells of the placental chorionic villi and trophoblasts, also bound anti-PAA. Of all lymphoid and nonlymphoid cell lines examined, only chronic lymphocytic leukemia (CLL) cells and some cell lines derived from Burkitt's lymphoma showed weak or no binding. This antibody also failed to react with a variety of nonprimate cell lines. Anti-PAA antibody did not immunoprecipitate any protein from lymphoid tumor cell lines to which it demonstrated a quantitatively high degree of binding, nor did protease treatment of these lines decrease antibody binding. Anti-PAA did, however, bind to glycolipids extracted from these cell lines. Binding of this monoclonal antibody to a minor neutral glycolipid, isolated from the erythroleukemia cell line K562, was about sixfold greater than that of any other K562 neutral glycolipid or ganglioside. Anti-PAA demonstrated weak or undetectable binding to purified, predominant, lymphoid cell membrane's neutral glycolipids and gangliosides. The monoclonal antibody anti-PAA appeared, therefore, to recognize a unique, proliferation-associated, neutral glycolipid present on normal as well as on benign and malignant proliferating cells. The antigen appeared to be universally expressed on proliferating cells from all human tissues with the exception of some Burkitt's cell lines and CLL cells. Nonhuman cell lines, except those for closely related primates, did not express PAA.
Travel-associated legionnaires’ disease in Europe: 2004
Authors: K D Ricketts, B McNaught, C A Joseph
Journal: Eurosurveillance (2006)

Six hundred and fifty five cases of travel-associated legionnaires’ disease with onset in 2004 have been reported to the EWGLINET surveillance scheme by 25 countries. A total of 84.9% of cases were diagnosed by the urinary antigen test, and 37 cultures were obtained. Thirty seven deaths were reported, giving a case fatality rate of 5.6%. Eighty six new clusters were detected, 45% of which would not have been detected without the EWGLINET scheme. Ninety four accommodation sites were investigated and the names of four sites were published on the EWGLI website. Fifteen sites were associated with additional cases after a report was received to say that investigations and control measures had been satisfactorily carried out. Further improvements could be made in the data collected on deaths due to travel-associated legionnaires’ disease, and on the number of samples taken for culture throughout Europe.
SPARC Expression Did Not Predict Efficacy of <i>nab</i>-Paclitaxel plus Gemcitabine or Gemcitabine Alone for Metastatic Pancreatic Cancer in an Exploratory Analysis of the Phase III MPACT Trial
Authors: Manuel Hidalgo, Carlos Plaza, Monica Musteanu, Peter Illei, Carrie B. Brachmann, Carla Heise, Daniel Pierce, Pedro P. Lopez-Casas, Camino Menendez, Josep Tabernero, Alfredo Romano, Xinyu Wei, Fernando Lopez-Rios, Daniel D. Von Hoff
Journal: Clinical Cancer Research (2015)

Abstract Purpose: nab-Paclitaxel plus gemcitabine was superior to gemcitabine alone for patients with metastatic pancreatic cancer (MPC) in the phase III MPACT trial. This study evaluated the association of secreted protein acidic and rich in cysteine (SPARC) levels with efficacy as an exploratory endpoint. Experimental Design: Patients with previously untreated MPC (N = 861) received nab-paclitaxel plus gemcitabine or gemcitabine alone. Baseline SPARC level was measured in the tumor stroma and epithelia (archival biopsies) and plasma. Experiments were performed in pancreatic cancer mouse models in which SPARC was intact or deleted. Results: SPARC was measured in the tumor stroma of 256 patients (30%), the tumor epithelia of 301 patients (35%), and plasma of 343 patients (40%). Stroma-evaluable samples were from metastases (71%), from the pancreas (11%), or of unidentifiable origin (insufficient tissue to determine; 17%). For all patients, stromal SPARC level [high (n = 71) vs. low (n = 185)] was not associated with overall survival (OS; HR, 1.019; P = 0.903); multivariate analysis confirmed this lack of association. There was no association between stromal SPARC level and OS in either treatment arm. Neither tumor epithelial SPARC nor plasma SPARC was associated with OS. Results from a SPARC knockout mouse model treated with nab-paclitaxel plus gemcitabine revealed no correlation between SPARC expression and tumor progression or treatment efficacy. Conclusions: SPARC levels were not associated with efficacy in patients with MPC. This exploratory analysis does not support making treatment decisions regarding nab-paclitaxel plus gemcitabine or gemcitabine alone in MPC based on SPARC expression. Clin Cancer Res; 21(21); 4811–8. ©2015 AACR.