tbuckley/cabot-search huggingface dataset:
The role of atypical respiratory pathogens in exacerbations of chronic obstructive pulmonary disease
Authors: B. M. W. Diederen, P. D. L. P. M. van der Valk, J. A. W. J. Kluytmans, M. F. Peeters, R. Hendrix
Journal: European Respiratory Journal (2007)

The aetiology of acute exacerbations of chronic obstructive pulmonary disease (COPD) is heterogeneous and still under discussion. Serological studies have suggested that Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila may play a role in acute exacerbations of COPD. The presence of these atypical pathogens in sputum samples was investigated in patients with stable COPD and with acute exacerbations of COPD using real-time PCR. The present study was part of a randomised, double-blind, single-centre study and a total of 248 sputum samples from 104 COPD patients were included. In total, 122 samples obtained during stable disease (stable-state sputa) and 126 samples obtained during acute exacerbations of COPD (exacerbation sputa) were tested. Of the 122 stable-state sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. Of the 126 exacerbation sputa, all samples were negative for M. pneumoniae and C. pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila DNA. The possible relationship between the presence of atypical pathogens and the aetiology of acute exacerbations in chronic obstructive pulmonary disease was investigated in patients with stable disease and in those with acute exacerbations using real-time PCR. No indication was found of a role for Legionella spp., Chlamydia pneumoniae or Mycoplasma pneumoniae in stable, moderately severe chronic obstructive pulmonary disease and in its exacerbations.
Zonal Heterogeneity for Gene Expression in Human Pancreatic Carcinoma
Authors: Toru Nakamura, Toshio Kuwai, Yasuhiko Kitadai, Takamitsu Sasaki, Dominic Fan, Kevin R. Coombes, Sun-Jin Kim, Isaiah J. Fidler
Journal: Cancer Research (2007)

Abstract Using Affymetrix HG-U133 Plus 2.0 array and laser capture microdissection techniques, we determined whether different zones of the same pancreatic tumor exhibited differential expression of genes. Human L3.6pl pancreatic cancer cells were implanted into the pancreas of nude mice. Three weeks later when tumors were 7 to 9 mm in diameter, gene expression patterns in tumor cells within the central and peripheral zones were compared, and 1,222 genes showed statistically significant differences. Bioinformatic functional analysis revealed that 346 up-regulated genes in the peripheral zone were related to cytoskeleton organization and biogenesis, cell cycle, cell adhesion, cell motility, DNA replication, localization, integrin-mediated signaling pathway, development, morphogenesis, and IκB kinase/nuclear factor-κB cascade; 876 up-regulated genes in the central zone were related to regulation of cell proliferation, regulation of transcription, transmembrane receptor protein tyrosine kinase signaling pathways, response to stress, small GTPase-mediated signal transduction, hexose metabolism, cell death, response to external stimulus, carbohydrate metabolism, and response to wounding. The reliability of the microarray results were confirmed by in situ hybridization analysis of the expression of two genes. Collectively, the data showed zonal heterogeneity for gene expression profiles in tumors and suggest that characterization of zonal gene expression profiles is essential if microarray analyses of genetic profiles are to produce reproducible data, predict disease prognosis, and allow design of specific therapeutics. [Cancer Res 2007;67(16):7597–604]
Echocardiographic Algorithm for Post–Myocardial Infarction LV Thrombus
Authors: Jonathan W. Weinsaft, Jiwon Kim, Chaitanya B. Medicherla, Claudia L. Ma, Noel C.F. Codella, Nina Kukar, Subhi Alaref, Raymond J. Kim, Richard B. Devereux
Journal: JACC. Cardiovascular imaging (2015)
EphB2 Expression across 138 Human Tumor Types in a Tissue Microarray: High Levels of Expression in Gastrointestinal Cancers
Authors: Alessandro Lugli, Hanspeter Spichtin, Robert Maurer, Martina Mirlacher, Jeff Kiefer, Pia Huusko, David Azorsa, Luigi Terracciano, Guido Sauter, Olli-P Kallioniemi, Spyro Mousses, Luigi Tornillo
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To comprehensively evaluate ephrin receptor B2 (EphB2) expression in normal and neoplastic tissues. EphB2 is a tyrosine kinase recently implicated in the deregulation of cell-to-cell communication in many tumors. Experimental Design: EphB2 protein expression was analyzed by immunohistochemistry on tissue microarrays that included 76 different normal tissues, &amp;gt;4,000 samples from 138 different cancer types, and 1,476 samples of colon cancer with clinical follow-up data. Results: We found most prominent EphB2 expression in the intestinal epithelium (colonic crypts) with cancer of the colorectum displaying the highest EphB2 positivity of all tumors. Positivity was found in 100% of 118 colon adenomas but in 33.3% of 45 colon carcinomas. EphB2 expression was also observed in 75 tumor categories, including serous carcinoma of the endometrium (34.8%), adenocarcinoma of the esophagus (33.3%), intestinal adenocarcinoma of the stomach (30.2%), and adenocarcinoma of the small intestine (70%). The occasional finding of strong EphB2 positivity in tumors without EphB2 positivity in the corresponding normal cells [adenocarcinoma of the lung (4%) and pancreas (2.2%)] suggests that deregulation of EphB2 signaling may involve up-regulation of the protein expression. In colon carcinoma, loss of EphB2 expression was associated with advanced stage (P &amp;lt; 0.0001) and was an indicator of poor overall survival (P = 0.0098). Conclusions: Our results provide an overview on the EphB2 protein expression in normal and neoplastic tissues. Deregulated EphB2 expression may play a role in several cancer types with loss of EphB2 expression serving as an indicator of the possible pathogenetic role of EphB2 signaling in the maintenance of tissue architecture of colon epithelium.
Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF- B, as a strategy for chemoprevention and therapy of adult T-cell leukemia
Authors: Mariko Watanabe, Takeo Ohsugi, Momoko Shoda, Takaomi Ishida, Shigemi Aizawa, Masae Maruyama-Nagai, Atae Utsunomiya, Shin Koga, Yasuaki Yamada, Shimeru Kamihira, Akihiko Okayama, Hiroshi Kikuchi, Kimiharu Uozumi, Kazunari Yamaguchi, Masaaki Higashihara, Kazuo Umezawa, Toshiki Watanabe, Ryouichi Horie
Journal: Blood (2005)
Prediction of battery depletion in implanted pacemakers
Authors: G. Davies, H. Siddons
Journal: Thorax (1973)

By the use of a measuring oscilloscope and the standard electrocardiogram limb leads the degree of battery depletion in an implanted pacemaker can be estimated. A formula based on readings obtained by this means has been used to determine when Devices fixed rate pacemakers should be removed. Laboratory tests show that 90% of their useful life is obtained by this means and it proved possible to extend the period of implantation from an arbitrary 24 months to 25 to 34 months without failure from battery depletion.
Determinants of end-systolic pressure-volume relations during acute regional ischemia in situ.
Authors: D A Kass, P Marino, W L Maughan, K Sagawa
Journal: Circulation (1989)

The influence of extent and location of regional ischemia, baseline left ventricular systolic function, and autonomic reflexes on in situ left ventricular end-systolic pressure-volume relations (ESPVRs) during coronary occlusion were studied in 13 open-chest dogs. Circumflex or left anterior descending arteries were randomly occluded (at proximal or distal sites) for 3 minutes in reflex-blocked (n = 6, hexamethonium/vagotomy) and unblocked (n = 7) animals. Pressure-volume data were obtained by the conductance-catheter technique, with ESPVRs determined by transient inferior vena caval occlusion. Ischemic zone size was estimated for each occlusion by radiolabeled microspheres. The relative influence of each variable on ESPVR change with ischemia was determined by multiple regression analysis. As in previous studies, regional ischemia displaced ESPVRs to the right by an amount that varied directly with ischemic bed size (y = +0.48x, r = 0.76, p less than 0.001). However, in contrast to previous data, coronary occlusion also reduced the ESPVR slope (end-systolic elastance, Ees) in the majority of cases. The extent of slope change was primarily dependent on the baseline elastance (Eesbase), such that the higher the initial elastance, the larger its subsequent reduction for any amount of ischemia (delta Ees = -0.78Eesbase, r = 0.94, p less than 0.001). Active reflexes added an offset constant to this relation (+3.15 mm Hg/ml, p less than 0.001). In addition, Ees fell slightly more with larger ischemic regions. Thus, although previous studies have reported primarily rightward parallel shifts in ESPVR with regional ischemia, the present data also demonstrate that the slope of the relation is often reduced. Greater baseline elastances typical of in situ, as opposed to isolated, ventricles probably explain the differences in apparent responses.
Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes
Authors: Gorica Nikoloski, Saskia M C Langemeijer, Roland P Kuiper, Ruth Knops, Marion Massop, Evelyn R L T M Tönnissen, Adrian van der Heijden, Theresia N Scheele, Peter Vandenberghe, Theo de Witte, Bert A van der Reijden, Joop H Jansen
Journal: Nature Genetics (2010)
Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a
Authors: Alfonso Quintás-Cardama, Omar Abdel-Wahab, Taghi Manshouri, Outi Kilpivaara, Jorge Cortes, Anne-Laure Roupie, Su-Jiang Zhang, David Harris, Zeev Estrov, Hagop Kantarjian, Ross L. Levine, Srdan Verstovsek
Journal: Blood (2013)
Adverse Effect of Adjuvant Tamoxifen in Premenopausal Breast Cancer with <i>Cyclin D1</i> Gene Amplification
Authors: Karin Jirström, Maria Stendahl, Lisa Rydén, Åsa Kronblad, Pär-Ola Bendahl, Olle Stål, Göran Landberg
Journal: Cancer Research (2005)

Abstract Cyclins D1 and A2 are cell cycle regulators that also have the ability to interact with the estrogen receptor (ER) and consequently interfere with antiestrogen treatment in breast cancer. Experimental data support this concept, but the clinical relevance needs to be further established. In this study, we evaluated cyclin D1 and A2 protein expression by immunohistochemistry and cyclin D1 gene (CCND1) amplification by fluorescence in situ hybridization in 500 primary breast cancers arranged in tissue microarrays. Patients had been randomized to 2 years of adjuvant tamoxifen or no treatment with a median follow-up of 14 years, allowing for subgroup analysis of treatment response defined by cyclin status. We found that both cyclin D1 and A2 protein overexpression was associated with an impaired tamoxifen response, although not significant in multivariate interaction analyses, whereas tamoxifen-treated patients with CCND1-amplified tumors had a substantially increased risk for disease recurrence after tamoxifen treatment in univariate analyses [relative risk (RR), 2.22; 95% confidence interval (95% CI), 0.94-5.26; P = 0.06] in contrast to nonamplified tumors (RR, 0.39; 95% CI, 0.23-0.65; P &amp;lt; 0.0001). Consequently, a highly significant interaction between tamoxifen treatment and CCND1 amplification could be shown regarding both recurrence-free survival (RR, 6.38; 95% CI, 2.29-17.78; P &amp;lt; 0.001) and overall survival (RR, 5.34; 95% CI, 1.84-15.51; P = 0.002), suggesting an agonistic effect of tamoxifen in ER-positive tumors. In node-positive patients, the disparate outcome according to gene amplification status was even more accentuated. In summary, our data implicate that despite a significant correlation to cyclin D1 protein expression, amplification status of the CCND1 gene seems a strong independent predictor of tamoxifen response, and possibly agonism, in premenopausal breast cancer.
Lamotrigine Dosing for Pregnant Patients With Bipolar Disorder
Authors: Crystal T. Clark, Autumn M. Klein, James M. Perel, Joseph Helsel, Katherine L. Wisner
Journal: American Journal of Psychiatry (2013)

Objective Little information is available on the need for dosage changes for lamotrigine in pregnant women with bipolar disorder. The authors present new data on serial serum levels of lamotrigine in pregnant patients on lamotrigine monotherapy. They also review the epilepsy literature on use of lamotrigine during pregnancy. Method Lamotrigine serum samples were obtained from eight mother-infant pairs at different time points during pregnancy and the postpartum period. Results All of the women were taking lamotrigine throughout pregnancy. Serum-level-to-dose ratios were lower during pregnancy than the postpartum period. Lamotrigine was taken once daily in doses ranging from 100 mg to 300 mg. Three patients had an increase of 50 mg to their daily dose across pregnancy. The change in serum lamotrigine levels in the postpartum period ranged from a 30% decrease to a 640% increase compared with the first level obtained during pregnancy. Level-to-dose ratios obtained within 4 weeks after delivery reflected a mean level 402% greater than the baseline level during gestation. Compared with the third trimester, lamotrigine serum concentration increased an average of 154% within 5 weeks after delivery. The most dramatic increase in lamotrigine serum level early after delivery occurred at 1.5 weeks. The mean infant cord level was 66% of the maternal serum level at delivery. The mean breast-fed infant serum level was 32.5% of the maternal serum levels. Conclusions The pattern of lamotrigine changes during pregnancy in these women with bipolar disorder was consistent with that described in the epilepsy literature.
C-Reactive Protein Enhances LOX-1 Expression in Human Aortic Endothelial Cells
Authors: Ling Li, Nadia Roumeliotis, Tatsuya Sawamura, Geneviève Renier
Journal: Circulation Research (2004)

C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful predictor of cardiovascular events. Recent data suggest that CRP may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endothelial receptor for oxLDL that plays a pivotal role in oxLDL-induced endothelial dysfunction. Whether CRP may regulate endothelial LOX-1 and induce endothelial dysfunction through this receptor is unknown. In the present study, we studied the in vitro effect of CRP on LOX-1 expression in human aortic endothelial cells (HAECs) and the role of LOX-1 in CRP-induced human monocyte adhesion to endothelium and oxLDL uptake by endothelial cells. Incubation of HAECs with CRP enhanced, in a dose- and time-dependent manner, LOX-1 mRNA and protein levels. Induction of LOX-1 protein was already present at 5 microg/mL CRP and reached a maximum at 25 microg/mL. This effect was reduced by antibodies against CD32/CD64, endothelin-1 (ET-1) and interleukin-6 (IL-6). The extent of stimulation of LOX-1 achieved by CRP was comparable to that elicited by high glucose and IL-6 and remained unchanged in presence of these factors. Finally, CRP increased, through LOX-1, both human monocyte adhesion to endothelial cells and oxLDL uptake by these cells. We conclude that CRP enhances endothelial LOX-1 expression and propose a new mechanism by which CRP may promote endothelial dysfunction, that of inducing LOX-1.
Changes in the Prevalence of the Most Common Causes of Chronic Liver Diseases in the United States From 1988 to 2008
Authors: Zobair M. Younossi, Maria Stepanova, Mariam Afendy, Yun Fang, Youssef Younossi, Hesham Mir, Manirath Srishord
Journal: Clinical Gastroenterology and Hepatology (2011)
Evidence That Transfer of Functional p53 Protein Results in Increased Apoptosis in Prostate Cancer
Authors: Louis L. Pisters, Curtis A. Pettaway, Patricia Troncoso, Timothy J. McDonnell, L. Clifton Stephens, Christopher G. Wood, Kim-Anh Do, Shawn M. Brisbay, Xuemei Wang, Elizabeth A. Hossan, Robert B. Evans, Cindy Soto, Marc G. Jacobson, Karen Parker, James A. Merritt, Mitchell S. Steiner, Christopher J. Logothetis
Journal: Clinical Cancer Research (2004)

Abstract Purpose: INGN 201 (Ad-p53) is a replication-defective adenoviral vector that encodes a wild-type p53 gene driven by the cytomegalovirus promoter. INGN 201 has been shown to have antitumoral activity against human prostate cancer cell lines. This study was undertaken to determine the safety of INGN 201 in patients with locally advanced prostate cancer, to assess transgene expression, and to evaluate antitumoral activity. Experimental Design: Our study included patients with clinical stage T3, T1c-T2a with Gleason score 8–10 disease, or T2a-T2b with Gleason score 7 disease and a prostate-specific antigen level &amp;gt;10 ng/ml. INGN 201 was administered by intraprostatic injection under ultrasonographic guidance. One course of INGN 201 was defined as three separate INGN 201 administrations 2 weeks apart. Biopsies at baseline and 24 h after the first administration were assessed for p53 protein by immunohistochemical staining and for apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Results: A total of 38 courses of INGN 201 gene therapy were administered to 30 patients, of whom 26 underwent radical prostatectomy. There were no grade 3 or 4 adverse events related to INGN 201 administration. Of the 11 patients with negative baseline immunostaining for p53 protein, 10 had positive p53 immunostaining after the first administration of INGN 201, and 8 had an increase in apoptotic cells by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. All 26 of the patients who underwent radical prostatectomy had significant residual viable prostate cancer, and 12 have experienced biochemical failure (median follow-up, 42 months). Conclusion: Intraprostatic INGN 201 gene therapy is safe and can reliably result in p53 protein production and apoptosis.
Frontiers of Biomedical Imaging Science 2009: Workshop Report and Research Opportunities
Authors: Thomas E. Yankeelov, Malcolm J. Avison, Bruce M. Damon, H. Charles Manning, Todd E. Peterson, John C. Gore
Journal: Cancer Research (2009)

The second “Frontiers of Biomedical Imaging Science” conference was held at Vanderbilt University in Nashville, TN from June 2 to 5, 2009. The impetus for the “Frontiers” conferences is that current specialized meetings focus mainly on a single modality and/or disease entity, limiting the
C<scp>ODING OF</scp> A<scp>UDITORY</scp> S<scp>PACE</scp>
Authors: Masakazu Konishi
Journal: Annual Review of Neuroscience (2003)

▪ Abstract Behavioral, anatomical, and physiological approaches can be integrated in the study of sound localization in barn owls. Space representation in owls provides a useful example for discussion of place and ensemble coding. Selectivity for space is broad and ambiguous in low-order neurons. Parallel pathways for binaural cues and for different frequency bands converge on high-order space-specific neurons, which encode space more precisely. An ensemble of broadly tuned place-coding neurons may converge on a single high-order neuron to create an improved labeled line. Thus, the two coding schemes are not alternate methods. Owls can localize sounds by using either the isomorphic map of auditory space in the midbrain or forebrain neural networks in which space is not mapped.
NF90 regulates inducible IL-2 gene expression in T cells
Authors: Lingfang Shi, Wayne R. Godfrey, Joseph Lin, Guohua Zhao, Peter N. Kao
Journal: The Journal of Experimental Medicine (2007)

Activation of T cells induces the production of T cell growth and survival factor interleukin (IL) 2. Regulatory T cells intrinsically fail to induce IL-2 expression upon activation and can suppress IL-2 production in conventional T cells. Thus, the control of IL-2 expression is critically important to T cell immune responses, yet the mechanisms remain incompletely understood. Nuclear factor (NF) 90 is a zinc-finger DNA- and double-stranded RNA-binding protein subunit that binds specifically to the antigen receptor response element (ARRE)/NF of activated T cells target sequence in the IL-2 proximal promoter. Inducible binding of NF90 to the IL-2 promoter in vivo is shown by chromatin immunoprecipitation. NF90 gene-targeted mice exhibit perinatal lethality. Compared with newborn NF90+/+ mice, newborn NF90−/− mice demonstrate severe impairment of IL-2 expression. Compared with wild-type cells, T cells deficient in NF90 are impaired in ARRE and IL-2 transcriptional activation and IL-2 mRNA stabilization. Fetal liver cells from NF90 gene-targeted mice were transplanted into irradiated adult recombination activating gene (RAG)–2−/− and IL-2Rγ−/− mice deficient in T cells, B cells, and natural killer cells. NF90+/+- and NF90−/−-RAG chimeric mice showed grossly normal repopulation of the thymus and spleen, but only NF90−/− T cells were severely impaired in IL-2 gene expression. Compared with littermates, NF90−/− RAG chimeric mice exhibited profound T cell lymphocytopenia in the peripheral circulation. Thus, NF90 regulates inducible IL-2 transcription, mRNA stability, and gene expression in T cells and represents a novel therapeutic target for the modulation of T cell immune responses.
Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase
Authors: Sophie Richard, Safa Moslemi, Herbert Sipahutar, Nora Benachour, Gilles-Eric Seralini
Journal: Environmental Health Perspectives (2005)

Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.