tbuckley/cabot-search huggingface dataset:
Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study
Authors: Anne-Marie Schjerning Olsen, Jesper Lindhardsen, Gunnar H Gislason, Patricia McGettigan, Mark A Hlatky, Emil Fosbøl, Lars Køber, Christian Torp-Pedersen, Morten Lamberts
Journal: BMJ (2015)

<b>Study question</b> What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? <b>Methods</b> This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. <b>Study answer and limitations</b> The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82 955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53 070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35 233) filled at least one prescription for NSAIDs and 45.5% (n=37 771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding. <b>What this study adds</b> In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. <b>Funding, competing interests, data sharing</b> AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.
Fibroblast heterogeneity in the diseased lung
Authors: Katharina Heinzelmann, Gerhard Preissler, Hauke Winter, Rudolf Hatz, Ina Koch, Michael Lindner, Jürgen Behr, Oliver Eickelberg
Journal: European Respiratory Journal (2014)

Chronic lung diseases (CLD), such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), are characterized by altered cellular composition and activation, as well as extracellular matrix (ECM) remodeling. Fibroblasts are thought to be the main ECM producing cell type in the lung. In this study, we hypothesized that different mesenchymal subpopulations within the human lung exhibit different surface marker profiles, and which might respond differentially to TGFbeta - a central key player in IPF and COPD.  Primary human fibroblasts were isolated from human lung parenchyma (n=5), taken in culture and treated with TGFbeta or left untreated for 48 hours. Western Blot (WB) and FACS analysis was performed to determine changes on the protein level and in the percentage of cells for ECM components and surface markers such as fibronectin, type I collagen, desmin, PDGFRα, CD90/Thy-1 and HMMR.  In FACS analysis 97% (±1.5) of fibroblasts were CD90/Thy-1 positive, whereas 57% (±12.8) were positive for fibronectin, 65% (±12.2) for type I collagen, 48% (±4.2) for desmin, 16% (±15.5) for PDGFRα and 7% (±5.8) for HMMR. After stimulating with TGFbeta, no changes on the protein level or in the percentage of cells could be detected for desmin (44% ±13.0) and CD90 (96% ±3.0), whereas a decrease could be observed for PDGFRa (0% ±0) as well as for HMMR (1% ±0.9), and an increase for fibronectin (80% ±8.0) and type I collagen (83% ±5.4). Similar results could be detected by WB.  In sum, we document that different subpopulations exist within the human lung, and which respond differentially to the growth factor TGFbeta in their marker expression. This indicates that different fibroblast subtypes play distinct roles in COPD or IPF.
Phytohemagglutinin Unresponsiveness in Mouse Spleen Cells Induced by Methylcholanthrene Sarcomas
Authors: William H. Adler, Tomoo Takiguchi, Richard T. Smith
Journal: Cancer Research (1971)

Summary  The composition of spleen cell populations and the response of spleen cells  in vitro  to phytohemagglutinin (PHA) were studied in mice bearing methylcholanthrene-induced sarcomas and mice immunized with membrane antigen. With the use of discontinuous albumin density gradients to separate spleen cell suspensions, it was found that tumor-bearing mice and immunized mice had a shift in their spleen cell population, with a depletion of the dense, small lymphocyte population and a majority representation of a less dense, large mononuclear cell population.  The PHA reactivity of the spleen cells from the tumor-bearing and immunized mice was less than normal. This finding correlated with the shift in the spleen cell population because the less dense cell types respond minimally to PHA. In mice in which the tumors were excised, the PHA response of the whole spleen cell population returned to normal.  Our findings with the tumor-bearing mice suggest that a poor response to PHA may not be indicative of an immune deficiency but rather may demonstrate the possibility that the mice are undergoing an active immune response to their tumors. In human cancer patients, a poor peripheral lymphocyte response to PHA and an inability to demonstrate delayed hypersensitivity reactions have been interpreted as indication of an immune deficiency. However, it could be speculated that these findings in these patients may also suggest the presence of an active immune response to their tumors, rather than an immune deficiency. At present, this speculation provides a different working hypothesis for the evaluation of the immune status of cancer patients.
Brief Report: Anti–Citrullinated Protein Antibody Positivity Correlates With Cartilage Damage and Proteoglycan Levels in Patients With Rheumatoid Arthritis in the Hand Joints
Authors: Nina Renner, Gerhard Krönke, Jürgen Rech, Michael Uder, Rolf Janka, Lars Lauer, Dominik Paul, Barbara Herz, Philipp Schlechtweg, Friedrich Frank Hennig, Georg Schett, Götz Welsch
Journal: Arthritis & Rheumatology (2014)

Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA) Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level. Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (≥3 years) and those with ACPA positivity than those with a short disease duration (<3 years)(p=0.034) or negative ACPA (p=0.0002), respectively. In contrast, no association between cartilage proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found. Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA.
Bosutinib is safe and active in patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML) with resistance or intolerance to imatinib and other tyrosine kinase inhibitors
Authors: T. H. Bruemmendorf, F. Cervantes, D. Kim, M. Chandy, T. Fischer, A. Hochhaus, D. Liu, G. J. Ossenkoppele, B. Hewes, J. E. Cortes
Journal: Journal of Clinical Oncology (2008)

7001 Background: Bosutinib (SKI-606), is an orally bioavailable dual Src/Abl inhibitor, 200 times as potent as imatinib, with minimal inhibitory activity against platelet-derived growth factor receptor or c-kit. Method: The phase II portion of a Phase I/II study to investigate the efficacy and safety of bosutinib in (pts) with CP CML who failed imatinib is ongoing. Results: We report preliminary data for 152 pts, median duration of treatment 2.82 mos (range 0.03–19.5 mos). Prior therapy in addition to imatinib, included interferon (58 pts), dasatinib and/or nilotinib (37 pts), and stem cell transplant (8 pts). Among pts who failed imatinib, 116 (76%) were imatinib-resistant and 36 (24%) intolerant. Of 38 pts evaluable for hematological response, 34 (89%) had complete response (CHR). 23/56 (41%) evaluable pts achieved a major cytogenetic response (MCyR), 17 (30%) of which were complete (CCyR). Of 58 pts evaluable for molecular response, 19 (33%) achieved a major molecular response, 11 (19%) of which were complete. Among pts with prior nilotinib or dasatinib exposure, 10/13 (77%) achieved CHR, 2/10 (20%) MCyR and 4/ 25 (16 %) major molecular response. 19 different mutations were found in 37 pts of 104 tested. CHR occurred in 2/2 pts with P-loop, 9/13 with non-P-loop and 23/26 with no mutations; MCyR occurred in 2/5 pts, 8/17 and 13/31 pts, respectively. The most common adverse events were gastrointestinal (nausea, vomiting, diarrhea), usually grade 1–2, manageable and improved spontaneously after 3- 4 weeks. Grade 3–4 non-hematologic toxicities (>5% of pts) were diarrhea (n=10, 7%) and rash (n=10, 7%). Grade 3–4 hematologic laboratory abnormalities were: thrombocytopenia (n=21, 14%), neutropenia (n=13, 9%), and anemia (2 pts, 1%). Other grade 3–4 laboratory abnormalities (>5% of pts,) included increased ALT (n=10, 7%) and hypophosphatemia (n=11, 7%). Conclusion: Bosutinib is an active treatment for pts with chronic phase CML who failed prior imatinib or other TKI therapy, including patients with a wide variety of Bcr-Abl kinase domain mutations. Bosutinib demonstrated a favorable toxicity profile with minimal hematologic toxicity. No significant financial relationships to disclose.
Briel Communication : Location by Immunoelectron Microscopy of Carcinoembryonic Antigen on Cultured Adenocarcinoma Cells 2
Authors: Ronald B. Herberman, Tadao Aoki, Grace Cannon, Margaret Liu, Macie Sturm
Journal: JNCI Journal of the National Cancer Institute (1975)

The tissue-culture cell line HT-29, derived from a primary colon adenocarcinoma and previously shown to secrete carcinoembryonic antigen (CEA), was examined by immunoelectron microscopy for the location of CEA in relation to the cells. CEA was closely adjacent to the plasma membrane, a location indistinguishable from that of alloantigens and other tumor-associated antigens.
Increased serum levels of soluble IL-18 receptor complex in allergic asthma
Authors: Shinichi Takenaka, Haruki Imaoka, Masanobu Matsuoka, Yoichiro Kaku, Hanako Oda, Tomotaka Kawayama, Tomoaki Hoshino
Journal: European Respiratory Journal (2013)

Introduction  IL-18 is known to play an important role in Th1/Tc1 polarization, and promoting the production of Th2 cytokines (e.g. IL-4, IL-5, IL-9, and IL-13) by T cells, NK cells, basophils, and mast cells. Recent studies have reported that IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including bronchial asthma, COPD, and lung fibrosis.  Aim  We reported that serum levels of IL-18 were significantly higher in the asthmatic subjects, when compared to either the non-asthmatic allergic subjects, or the healthy controls. However the roles of soluble IL-18 receptor complex (sIL-18R) in allergic asthma remain unclear. Therefore, in this study we measured serum levels of sIL-18R in patients with allergic asthma.  Method  We obtained sera from age-matched 19 allergic asthmatic subjects, 14 allergic non-asthmatic subjects, and 14 healthy controls. We measured serum levels of sIL-18R by using ELISA system.  Result  The serum levels of sIL-18R in allergic asthmatics (32.9±4.3 ng/ml) were significantly higher than those in non-asthmatic allergic subjects (18.8±1.5 ng/ml) and healthy controls (16.1±1.6 ng/ml). In the entire population, there was a significant correlation between serum sIL-18R levels and the levels of IgE.  Conclusion  sIL-18R may play an important role in the inflammatory process of allergic asthma.
Abstract 05: Longer Duration of Obesity Beginning in Young Adulthood is Associated with Greater Left Ventricular Mass and Worse Left Ventricular Function in Middle-Age: The CARDIA Study
Authors: Jared P Reis, Norrina B Allen, Bethany Barone-Gibbs, Joyce M Lee, Cora E Lewis, Joao Lima, Donald Lloyd-Jones, Catherine M Loria, Tiffany M Powell-Wiley, Gina Wei, Kiang Liu
Journal: Circulation (2014)

Background: As a result of the obesity epidemic, individuals are becoming obese at a younger age than in previous generations. Yet, few studies have determined the consequences of a longer duration of obesity. The present study examined whether the duration of obesity beginning early in adulthood is associated with left ventricular (LV) structure and function in middle-age. Methods: We studied 2,545 white and black adults aged 18-30 years without obesity [body mass index (BMI) &lt;30 kg/m 2 ] at baseline in 1985-86 or clinically apparent heart disease through year 25 (2010-11) in the multicenter, community-based CARDIA study. Duration of obesity (years with BMI ≥30.0 kg/m 2 ) was calculated using repeat measurements of BMI performed 2, 5, 7, 10, 15, 20, and 25 years after baseline. Outcomes included LV mass and ejection fraction from an echocardiogram performed during the 25-year follow-up examination. Results: During follow-up, 994 participants became obese (39.1%); mean duration of obesity was 14.1 years. After adjustment for demographic and behavioral covariates, including year 25 BMI, a longer duration of obesity was associated with a greater LV mass and a lower ejection fraction (Table, model 1). Further adjustment for intermediate clinical covariates, including antihypertensive medication use, systolic blood pressure, heart rate, and diabetes only modestly attenuated these associations (Table, model 2). These associations were similar across white and black men and women (p-interaction&gt;0.10, for all). Conclusions: Longer duration of obesity from young adulthood to middle-age was associated with significantly greater LV mass and marginally lower LV function in midlife, independent of concurrent BMI.
Comparative Audit: The Trouble with Possum
Authors: Simon D Bann, Sanjeev Sarin
Journal: Journal of the Royal Society of Medicine (2001)

The Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) has been proposed for use in comparative audit between surgeons and between hospitals. To assess its feasibility, POSSUM scoring was attempted on admission in all patients under the care of two consultant surgeons over a six-month period. Scores were awarded only if all investigations necessary for POSSUM were performed; investigations unnecessary for effective treatment were not performed. 815 patient discharges were recorded over the six-month period, with 521 patients undergoing operative procedures. Of those undergoing an operation, scores could be allocated in only 155 (30%). Scoring systems such as POSSUM are procedure-based, thereby excluding those who do not undergo an operation. However, most of our operative cases were also excluded. Full POSSUM scoring will often require additional investigations. POSSUM is unlikely to be of use in the wider setting of comparative audit.
Abstract P1-06-06: Meta-analysis reveal novel mechanism of bisphenol A effect on mammary gland
Authors: Xiang Gu, Hui Gao, Danhan Wang, Abhik Bandyopadhyay, Qiaoxiang Dong, LuZhe Sun
Journal: Cancer Research (2015)

Abstract Pubertal exposure to bisphenol A (BPA) has been shown to cause abnormal mammary gland development and neoplastic transformation in adults. However, the mechanism of this BPA effect still remains largely unknown. We exposed 21-day-old Balb/c mice to BPA by gavage (25 µg/kg/day) during puberty for 3 weeks. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age and subsequently sorted into Lin-CD49f-CD24-stromal cells, Lin-CD49fhighCD24med MaSCs-enriched basal cells and Lin-CD49flowCD24high luminal progenitor-enriched cells with FACS for gene expression analysis. The Gene Ontology (GO) Enrichment Analysis shows that upon BPA treatment, the biological processes (BPs) significantly enriched in luminal compartment were related to response to organic substance and hormone stimuli at early stage (2 month old) whereas to cell cycle regulation at late stage (4 month old), consistent with published study in mammary gland morphology where BPA promoted the expansion of luminal population. However, the BPs enriched in spheres derived from basal cells (highly enriched with MaSCs) collected at late stage (4 month old) were mainly related to cell adhesion, epithelial differentiation and in stromal cells were related with vascular development for tissues collected either immediately after BPA treatment or 6 weeks later at 4-month of age. More interestingly, the Downstream Function Effects Analysis performed by Ingenuity Pathway Analysis reveal the changes in any compartments will all lead to significant activation of cancer-related downstream effects including hyperplasia, neoplasm of mammary tumor, proliferation of tumor cells and invasion of breast cancer, although there are few overlapping common genes in these compartments and conditions upon BPA treatment, indicating the different mechanism in response to BPA treatment and tumorigenesis. Network analysis revealed that the potential upstream regulators for these enriched BPs are TGFβ1, VEGF, PPARG, Estrogen/ Estrogen Receptor, glucocorticoid, ERK and NOTCH signaling. Together with our recently published data, this study reveals the difference in immediate and delayed response to pubertal BPA treatment and indicates that cross-talk between several growth factor and hormonal receptor signaling pathways may contribute to the altered cellular processes by BPA, consistent with the role of BPA as an endocrine disruptor. Citation Format: Xiang Gu, Hui Gao, Danhan Wang, Abhik Bandyopadhyay, Qiaoxiang Dong, LuZhe Sun. Meta-analysis reveal novel mechanism of bisphenol A effect on mammary gland [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-06-06.
Bactericidal activity of ciprofloxacin dry powder for inhalation (DPI) in a hollow fiber (HF) model
Authors: Sabine Obertegger, Gabriele Weskott, Petra Surdakowski, Karina Merfort, Martin Glenschek-Sieberth
Journal: European Respiratory Journal (2014)

Background:  Ciprofloxacin DPI is in Phase III development for chronic intermittent treatment of non-cystic fibrosis bronchiectasis (NCFB) patients.  Objective:  To assess the bactericidal activity of Ciprofloxacin DPI against clinical respiratory pathogens in a HF system.  Methods:  Recent respiratory isolates of ciprofloxacin-susceptible  H. influenzae ,  K. pneumoniae ,  S. aureus  (1 each), and 3  P. aeruginosa  (minimum inhibitory concentrations [MICs] of 0.12, 0.5, and 1.0mg/L) were cultured in a HF system and exposed to ciprofloxacin at levels simulating the mean sputum concentration profile after patient inhalation of Ciprofloxacin DPI 32.5mg. Colony-forming units (CFUs) and MICs were measured during a 5-day bid treatment course and 5 days of untreated follow-up.  Results:  Rapid bactericidal killing of all organisms was observed within 10 hours of first treatment and bacterial populations were reduced below the limit of detection (10 CFU/mL) during treatment. In the follow-up phase, no regrowth was observed for  H. influenzae  or the  P. aeruginosa  isolate with MIC of 0.12mg/L. Remaining isolates showed regrowth without elevated MICs. There were no changes in resistance frequency at ciprofloxacin doses of 3X and 5X MIC compared with untreated isolates.  Conclusion:  In this  in vitro  infection model, Ciprofloxacin exhibited bactericidal activity against clinical respiratory pathogens at concentrations achieved in human sputum after inhalation of Ciprofloxacin DPI. Isolates that regrew did not show elevated MICs or increased resistance, suggesting that Ciprofloxacin DPI does not promote resistance development. Clinical data in NCFB patients are required to confirm results.
Reevaluation of Relationship Between C Chromosome Marker and Epstein-Barr Virus: Chromosome and Immunofluorescence Analyses of 16 Human Hematopoietic Cell Lines<xref ref-type="fn" rid="FN2">2</xref>
Authors: C. C. Huang, J. Minowada, R. T. Smith, B. O. Osunkoya
Journal: JNCI Journal of the National Cancer Institute (1970)

The chromosomes of 16 cell lines derived from Burkitt lymphomas and from leukocytes of patients with infectious mononucleosis (IM) were either pseudodiploid (4 Burkitt lines) or diploid (12 IM lines). By an indirect immunofluorescent technique, a low percentage of cells containing Epstein-Barr virus (EBV) was detected in all but 1 IM line. A search for cells with 1 or more C chromosome(s) possessing a subterminal secondary constriction, as has been suggested to be associated with the presence of EBV, revealed 1 EBV-negative IM line and 2 EBV-positive IM lines having low incidences of cells with the C chromosome marker, 1% in 2 lines and 4% in the third. The last line also had a high incidence of lesions in other chromosomes. Lesions among the various groups of chromosomes of this IM line were randomly distributed, but the terminal or subterminal regions of the chromosomes of the A, B, and C groups, especially in the long arms, accumulated more lesions than did the other regions of the chromosomes. In 3 of the 4 Burkitt lines, specific lesions in 1 chromosome of the A group are common. In 1 line, a subterminal secondary constriction in the long arm of A2 was seen in 95% of the cells examined; in the other 2 lines, subterminal secondary constrictions or subterminal chromatid and chromosome gaps in 1 chromosome of group A, possibly A1, were found in 12 and 26%, respectively, of the cells examined. The results of the present study, as well as those of others, suggest that EBV can induce chromosome injuries in certain hematopoietic cell lines, and that the terminal and subterminal regions of the chromosomes are vulnerable to infection with the virus, but that there seems to be no apparent association between the presence of EBV and the C chromosome marker.