tbuckley/cabot-search huggingface dataset:
Glycation, Inflammation, and RAGE
Authors: Shi Fang Yan, Ravichandran Ramasamy, Yoshifumi Naka, Ann Marie Schmidt
Journal: Circulation Research (2003)

The cardiovascular complications of diabetes represent the leading cause of morbidity and mortality in affected subjects. The impact of hyperglycemia may be both direct and indirect: indirect consequences of elevated blood glucose lead to generation of advanced glycation endproducts, the products of nonenzymatic glycation/oxidation of proteins/lipids that accumulate in the vessel wall, and are signal transduction ligands for Receptor for AGE (RAGE). Although enhanced in diabetes, AGE accumulation also occurs in euglycemia and aging, albeit to lower degrees, driven by oxidant stress and inflammation. In hyperglycemia, production of 3-deoxyglucosone, at least in part via the polyol pathway, provides an amplification loop to sustain AGE generation, oxidant stress, and vascular activation. Furthermore, recruitment of inflammatory cells bearing S100/calgranulins, also ligands for RAGE, augments vascular dysfunction. We hypothesize that activation of RAGE is a final common pathway that transduces signals from these diverse biochemical and molecular species, leading to cardiovascular perturbation. Ultimately, these pathways synergize to construct a scaffold on which the complications of diabetes in the vasculature and heart may be built. We propose that antagonism of RAGE will provide a unique means to dismantle this scaffold and, thereby, suppress initiation/progression of vascular disease and cardiac dysfunction that accompany diabetes and aging.
Indacaterol, a novel inhaled 2-agonist, provides sustained 24-h bronchodilation in asthma
Authors: K. M. Beeh, E. Derom, F. Kanniess, R. Cameron, M. Higgins, A. van As
Journal: European Respiratory Journal (2007)

The present study examined the bronchodilator and safety profiles of single-dose indacaterol in intermittent or persistent asthma. In the present double-blind crossover study, 42 patients were randomised to receive single doses of indacaterol (50, 100, 200 and 400 µg) or placebo via a hydrofluoroalkane pressurised metered-dose inhaler. The primary efficacy comparisons were the per cent changes in forced expiratory volume in one second (FEV 1 ) between indacaterol and placebo 30 min and 21 h post-dose. All doses resulted in prolonged bronchodilation, with indacaterol 200 and 400 µg meeting pre-specified efficacy criteria. The mean percentage increases in FEV 1 from placebo with indacaterol 200 and 400 µg were 7.6 and 14.9%, respectively, at 30 min, and 7.5 and 10.4%, respectively, at 21 h post-dose. At these doses, changes in mean FEV 1 relative to placebo were statistically significant from 5 min to 25 h, inclusive. At 5 min, the geometric least squares mean values for FEV 1 were 3.08 and 3.22 L for the 200 and 400 µg doses, respectively, compared with 2.99 L for placebo. At 24 h after dosing, the baseline-adjusted geometric least square mean FEV 1 was 3.13, 3.11, 3.24 and 3.30 L for indacaterol 50, 100, 200 and 400 µg, respectively, and 2.98 L for placebo. All treatments were well tolerated. Once-daily indacaterol at doses of 200 and 400 µg provided sustained 24-h bronchodilation, with a rapid onset and a good tolerability and safety profile.
Integration of metabolite with transcript and enzyme activity profiling during diurnal cycles in Arabidopsis rosettes.
Authors: Yves Gibon, Bjoern Usadel, Oliver E Blaesing, Beate Kamlage, Melanie Hoehne, Richard Trethewey, Mark Stitt
Journal: Genome biology (2006)

Abstract Background Genome-wide transcript profiling and analyses of enzyme activities from central carbon and nitrogen metabolism show that transcript levels undergo marked and rapid changes during diurnal cycles and after transfer to darkness, whereas changes in activities are smaller and delayed. In the starchless pgm mutant, where sugars are depleted every night, there are accentuated diurnal changes in transcript levels. Enzyme activities in this mutant do not show larger diurnal changes; instead, they shift towards the levels found in the wild type after several days of darkness. This indicates that enzyme activities change slowly, integrating the changes in transcript levels over several diurnal cycles. Results To generalize this conclusion, 137 metabolites were profiled using gas and liquid chromatography coupled to mass spectroscopy. The amplitudes of the diurnal changes in metabolite levels in pgm were (with the exception of sugars) similar or smaller than in the wild type. The average levels shifted towards those found after several days of darkness in the wild type. Examples include increased levels of amino acids due to protein degradation, decreased levels of fatty acids, increased tocopherol and decreased myo-inositol. Many metabolite-transcript correlations were found and the proportion of transcripts correlated with sugars increased dramatically in the starchless mutant. Conclusion Rapid diurnal changes in transcript levels are integrated over time to generate quasi-stable changes across large sectors of metabolism. This implies that correlations between metabolites and transcripts are due to regulation of gene expression by metabolites, rather than metabolites being changed as a consequence of a change in gene expression.
Hendersonula toruloidea infection of the nails in Caucasians
Authors: S.K. Jones, J.E. White, P.H. Jacobs, C.R.C. Porter
Journal: British Journal of Dermatology (1984)

Journal Article Hendersonula toruloidea infection of the nails in Caucasians Get access S.K. Jones, S.K. Jones Department of Dermatology, Western Infirmary, Glasgow G11 6NT Search for other works by this author on: Oxford Academic Google Scholar J.E. White, J.E. White Department of Dermatology, Royal South Hants Hospital, Southampton Search for other works by this author on: Oxford Academic Google Scholar P.H. Jacobs, P.H. Jacobs Department of Mycology, Pathology Department, General Hospital, Southampton Search for other works by this author on: Oxford Academic Google Scholar C.R.C. Porter C.R.C. Porter Department of Mycology, Pathology Department, General Hospital, Southampton Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Page 22, https://doi.org/10.1111/j.1365-2133.1984.tb05241.x Published: 01 July 1984
Differential CD146 Expression on Circulating Versus Tissue Endothelial Cells in Rectal Cancer Patients: Implications for Circulating Endothelial and Progenitor Cells As Biomarkers for Antiangiogenic Therapy
Authors: Dan G. Duda, Kenneth S. Cohen, Emmanuelle di Tomaso, Patrick Au, Rachael J. Klein, David T. Scadden, Christopher G. Willett, Rakesh K. Jain
Journal: Journal of Clinical Oncology (2006)

Purpose Circulating endothelial cells (CECs) and progenitor cells are currently evaluated as potential biomarkers of antiangiogenic therapy. CD146 is considered a panendothelial-specific marker, but its utility as a CEC marker in cancer patients remains unclear. Patients and Methods We analyzed the expression of CD146 on mononuclear blood cells, primary tissue endothelial cells, and malignant and normal tissues by flow cytometric and immunohistochemical analyses. Furthermore, we measured the circulation kinetics of CD146 + cells before, and then 3 and 12 days after vascular endothelial growth factor (VEGF) antibody blockade by bevacizumab infusion in rectal cancer patients enrolled in a phase I trial. Results In the peripheral blood of these cancer patients, over 90% of the CD146 + cells were CD45 + hematopoietic cells. CD146 expression was primarily detected on a subset of CD3 + CD4 + lymphocytes, and was undetectable on CD34 + CD133 + CD45 dim progenitor cells or CD31 bright CD45 − viable CECs. In contradistinction, CD146 was detectable in tissues on both cellular components of tumor vessel wall: CD31 bright CD45 − endothelial cells and α-SMA + pericytes. Unlike viable CECs and progenitor cells, CD146 + cell concentration in the peripheral blood of cancer patients did not decrease during VEGF blockade. Conclusion CD146 is fairly homogeneously expressed on vascular endothelium but not on viable CECs or progenitor cells. The vast majority of CD146 + blood cells are lymphocytes, and VEGF blockade by bevacizumab did not significantly change their number in rectal cancer patients. These results underscore the need for further characterization and identification of new markers for CEC subpopulations for their development as biomarkers of antiangiogenic therapy.
Decreased Overall and Bladder Cancer–Specific Mortality with Adjuvant Chemotherapy After Radical Cystectomy: Multivariable Competing Risk Analysis
Authors: Michael Froehner, Rainer Koch, Ulrike Heberling, Vladimir Novotny, Sven Oehlschlaeger, Matthias Hübler, Gustavo B. Baretton, Oliver W. Hakenberg, Manfred P. Wirth
Journal: European Urology (2015)
Metyrapone-Inhibited Oncogenesis in Mice Inoculated With a Murine Sarcoma Virus2
Authors: Giuseppe Rettura, Joseph Seitter, Martin Zisblatt, Stanley M. Levenson, Norman Levine, Eli Seifter
Journal: JNCI Journal of the National Cancer Institute (1973)

Metyrapone fed to mice, 3 days before inoculation with murine sarcoma virus (MSV) of the Moloney strain and continued for the following 3 weeks, reduced the incidence and severity of tumor development. Similar results were obtained when metyrapone was fed to mice 3 days after inoculation. The action of metyrapone was probably nonspecific with respect to the virus, and the beneficial prophylactic action was probably due to the strengthening of the immune capabilities in the inoculated mice by metyrapone. This view is supported by data showing that metyrapone treatment causes thymic enlargement.
miRNAs: Small Genes with Big Potential in Metazoan Phylogenetics
Authors: James E. Tarver, Erik A. Sperling, Audrey Nailor, Alysha M. Heimberg, Jeffrey M. Robinson, Benjamin L. King, Davide Pisani, Philip C.J. Donoghue, Kevin J. Peterson
Journal: Molecular Biology and Evolution (2013)

microRNAs (miRNAs) are a key component of gene regulatory networks and have been implicated in the regulation of virtually every biological process found in multicellular eukaryotes. What makes them interesting from a phylogenetic perspective is the high conservation of primary sequence between taxa, their accrual in metazoan genomes through evolutionary time, and the rarity of secondary loss in most metazoan taxa. Despite these properties, the use of miRNAs as phylogenetic markers has not yet been discussed within a clear conceptual framework. Here we highlight five properties of miRNAs that underlie their utility in phylogenetics: 1) The processes of miRNA biogenesis enable the identification of novel miRNAs without prior knowledge of sequence; 2) The continuous addition of miRNA families to metazoan genomes through evolutionary time; 3) The low level of secondary gene loss in most metazoan taxa; 4) The low substitution rate in the mature miRNA sequence; and 5) The small probability of convergent evolution of two miRNAs. Phylogenetic analyses using both Bayesian and parsimony methods on a eumetazoan miRNA data set highlight the potential of miRNAs to become an invaluable new tool, especially when used as an additional line of evidence, to resolve previously intractable nodes within the tree of life.
Benzodithiophenes Potentiate Differentiation of Acute Promyelocytic Leukemia Cells by Lowering the Threshold for Ligand-Mediated Corepressor/Coactivator Exchange with Retinoic Acid Receptor α and Enhancing Changes in all-<i>trans</i>-Retinoic Acid–Regulated Gene Expression
Authors: Ke Xu, Fabien Guidez, Annegret Glasow, Danna Chung, Kevin Petrie, Kimberly Stegmaier, Kan-Kan Wang, Ji Zhang, Yongkui Jing, Arthur Zelent, Samuel Waxman
Journal: Cancer Research (2005)

Differentiation induction is an effective therapy for acute promyelocytic leukemia (APL), which dramatically responds to all-trans-retinoic acid (ATRA). Recent studies have indicated that combinatorial use of retinoid and nonretinoid compounds, such as histone deacetylase inhibitors, arsenics, and PKA agonists, has higher therapeutic value in this disease and potentially in other malignancies. In a screen of 370 compounds, we identified benzodithiophene analogues as potent enhancers of ATRA-induced APL cell differentiation. These effects were not associated with changes in global histone acetylation and, for the most potent compounds, were exerted at very low nanomolar concentrations, and were paralleled by enhancement of some, but not all, ATRA-modulated gene expressions. Investigating the mechanism underlying the effects of these drugs on ATRA-induced APL cell differentiation, we have shown that benzodithiophenes enhance ATRA-mediated dissociation and association of corepressor N-CoR and coactivator p300 acetyltransferase, respectively, with retinoic acid receptor (RAR) alpha proteins. These data suggest that benzodithiophenes act at the level of receptor activation, possibly by affecting posttranslational modification of the receptor (and/or coregulators), thus leading to an enhancement in ATRA-mediated effects on gene expression and APL cell differentiation. Given the specificities of these low benzodithiophene concentrations for PML-RARalpha and RARalpha, these drugs may be useful for combinatorial differentiation therapy of APL and possibly other acute myelogenous leukemia subtypes in which the overall ATRA signaling is suppressed.
Vaccination with the major secretory protein of Legionella pneumophila induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease.
Authors: S J Blander, M A Horwitz
Journal: The Journal of Experimental Medicine (1989)

We have examined the capacity of the major secretory protein (MSP) of Legionella pneumophila to induce humoral, cell-mediated, and protective immunity in a guinea pig model of Legionnaires' disease. MSP was purified to homogeneity by ammonium sulfate precipitation, molecular sieve chromatography, and ion-exchange chromatography. The purified MSP was nonlethal and nontoxic to guinea pigs upon subcutaneous administration. Guinea pigs immunized with a sublethal dose of aerosolized L. pneumophila or a subcutaneous dose of MSP developed a strong cell-mediated immune response to MSP. Such guinea pigs exhibited marked splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity to MSP in comparison with control animals. Guinea pigs immunized with MSP also developed a strong humoral immune response to MSP, as assayed by an ELISA. The median reciprocal antibody titer was 362 (range 45 to greater than 2,048) for immunized animals compared with less than 8 for controls. In contrast, guinea pigs immunized with a sublethal dose of L. pneumophila failed to develop anti-MSP antibody. Guinea pigs immunized with MSP and then challenged with a lethal aerosol dose of L. pneumophila exhibited highly significant protective immunity in each of five consecutive experiments. MSP induced protective immunity in dose-dependent fashion (40 greater than 10 greater than 2.5 greater than 0.6 micrograms MSP); vaccination with two doses of as little as 2.5 micrograms MSP induced significant protective immunity (p = 0.01, Fisher's Exact Test, two-tailed). Altogether, 21 (81%) of 26 animals immunized with 40 micrograms MSP survived challenge compared with 0 (0%) of 26 sham-immunized control animals (p = 7 x 10(-10), Fisher's Exact Test, two-tailed). MSP-immunized but not control guinea pigs were able to limit L. pneumophila multiplication in their lungs. This study demonstrates that (a) guinea pigs sublethally infected with L. pneumophila develop a strong cell-mediated immune response to MSP; (b) guinea pigs immunized with MSP develop a strong humoral and cell-mediated immune response to MSP; (c) guinea pigs immunized with MSP develop a very high level of protective immunity to lethal aerosol challenge with L. pneumophila; and (d) MSP-immunized animals are able to limit L. pneumophila multiplication in their lungs. MSP, an extracellular protein of an intracellular pathogen, has potential as a vaccine for the prevention of Legionnaires' disease. Secretory molecules of other intracellular pathogens may also have vaccine potential.
Autistic Social Impairment in the Siblings of Children With Pervasive Developmental Disorders
Authors: John N Constantino, Clara Lajonchere, Marin Lutz, Teddi Gray, Anna Abbacchi, Kathleen McKenna, Deepti Singh, Richard D Todd
Journal: American Journal of Psychiatry (2006)

Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investigated subsyndromal autistic impairments among siblings of probands with pervasive developmental disorders.The authors used the Social Responsiveness Scale to obtain quantitative assessments of autistic social impairment in three groups of proband-sibling pairs: 1) autistic children from multiple-incidence families and their closest in age nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental disorder, including autism, and their closest-in-age brothers (N=100 pairs), and 3) children with psychopathology unrelated to autism and their closest-in-age brothers (N=45 pairs).Sibling Social Responsiveness Scale scores were continuously distributed and substantially elevated for both the autistic and pervasive developmental disorder groups. Highest scores (i.e., greatest impairment) were seen among siblings of autistic probands from multiple-incidence families, followed by siblings of probands with any pervasive developmental disorder, then siblings of probands with psychopathology unrelated to autism.Taken together with previous findings, these results support the notion that genetic susceptibility factors responsible for common, subsyndromal social impairments may be related to the causes of categorically defined pervasive developmental disorders.
CT colonography for detection and characterisation of synchronous proximal colonic lesions in patients with stenosing colorectal cancer
Authors: Seong Ho Park, Ju Hee Lee, Seung Soo Lee, Jin Cheon Kim, Chang Sik Yu, Hee Cheol Kim, Byong Duk Ye, Mi-Jung Kim, Ah Young Kim, Hyun Kwon Ha
Journal: Gut (2011)

<h3>Objective</h3> To investigate CT colonography (CTC) performance for detecting and characterising synchronous lesions proximal to a stenosing colorectal cancer and to suggest patient management strategies according to the CTC findings. <h3>Methods</h3> 411 consecutive patients underwent CTC for proximal colonic evaluation after failed colonoscopy past a newly diagnosed stenosing colorectal cancer. Pathological examination of colectomy specimen and/or postsurgical colonoscopy with pathological confirmation of the proximal synchronous lesions to serve as reference standards existed in 284 patients. Per-patient and per-lesion diagnostic performance measures of CTC for diagnosing proximal synchronous lesions ≥6 mm analysed by histopathological categories were obtained for the 284 patients. Per-lesion sensitivity and positive predictive value (PPV) of various CTC lesion size criteria and lesion size combined with other CTC findings for diagnosing cancer in the proximal colon were determined. <h3>Results</h3> Both per-patient and per-lesion CTC detection sensitivities for proximal synchronous cancers were 100% (6/6 patients and 8/8 lesions; 95% CI 64.3% to 100% and 70.7% to 100%, respectively) with the corresponding per-patient negative predictive value (NPV) of a negative CTC of 100% (194/194 patients; 95% CI 98.3% to 100%). Per-patient NPV of a negative CTC for advanced neoplasia (ie, advanced adenomas and colorectal cancers) was 97.4% (189/194 patients; 95% CI 93.9% to 99.1%). A lesion size ≥15 mm on CTC as the criterion to specifically diagnose proximal cancer yielded 87.5% (7/8 lesions; 95% CI 50.8% to 99.9%) per-lesion sensitivity, rendering one 8-mm submucosal cancer mischaracterised as a non-cancerous lesion, and 70% (7/10 lesions; 95% CI 39.2% to 89.7%) per-lesion PPV. Additional CTC findings did not improve the sensitivity. <h3>Conclusion</h3> CTC is highly sensitive in detecting synchronous cancers proximal to a stenosing colorectal cancer. CTC has limited capability in differentiating advanced adenomas from colorectal cancer and this compromises the PPV of CTC for the presence of proximal cancer.
Early Renal Insufficiency and Hospitalized Heart Disease after Renal Transplantation in the Era of Modern Immunosuppression
Authors: Kevin C Abbott, Christina M Yuan, Allen J Taylor, David F Cruess, Lawrence Y C Agodoa
Journal: Journal of the American Society of Nephrology (2003)

Renal insufficiency has been identified as a risk factor for graft loss and death after renal transplantation but has not been consistently linked to early, nonfatal, hospitalized heart disease (HHD). With the United States Renal Data System database, 29,597 patients who received a kidney transplant between January 1, 1996, and July 31, 2000, with Medicare as the primary payer, and were monitored until December 31, 2000, were studied. Cox proportional-hazards regression models were used to calculate the association of recipient estimated GFR (eGFR) at 1 yr after renal transplantation, as determined with the Modification of Diet in Renal Disease formula, with hospitalization for treatment of acute coronary syndromes (ACS) (International Classification of Diseases, version 9, code 410.x or 411.x) or congestive heart failure (CHF) (code 428.x) 1 to 3 yr after renal transplantation. Rates of ACS and CHF were 2.2 and 4.9%, respectively, for patients with eGFR of <44.8 ml/min per 1.73 m(2), compared with 1.2 and 1.4% for patients with eGFR of >69.7 ml/min per 1.73 m(2). Reduced eGFR (<44.8 ml/min per 1.73 m(2), compared with >69.7 ml/min per 1.73 m(2)) at the end of the first 1 yr after transplantation was independently associated with increased risks of both ACS (adjusted hazard ratio, 2.16; 95% confidence interval, 1.39 to 3.35) and CHF (adjusted hazard ratio, 2.95; 95% confidence interval, 2.24 to 3.90). It was concluded that early renal insufficiency (approximately stage 3 chronic kidney disease) was associated with higher rates of HHD 1 to 3 yr after kidney transplantation. Preservation of renal function after renal transplantation may reduce the rates of HHD, and renal transplant recipients with reduced eGFR should be considered at high risk of developing cardiovascular disease.
Statutory Requirements for Disclosure of Breast Cancer Treatment Alternatives
Authors: S. G. Nayfield, G. C. Bongiovanni, M. H. Alciati, R. A. Fischer, L. Bergner
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Statutory Requirements for Disclosure of Breast Cancer Treatment Alternatives Get access Susan G. Nayfield, Susan G. Nayfield *Affiliations of authors: Community Oncology and Rehabilitation Branch Correspondence to : Susan G. Nayfield, M.D., M.Sc, National Institutes of Health, Executive Plaza North, Rm. 300, Bethesda, MD 20892. See “Notes” section following “References.” Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory C. Bongiovanni, Gregory C. Bongiovanni Vanderbilt University School of LawNashville, Tenn Search for other works by this author on: Oxford Academic PubMed Google Scholar Marianne Haenlein Alciati, Marianne Haenlein Alciati (Public Health Applications Research Branch), Division of Cancer Prevention and Control, National Cancer InstituteBethesda, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruth A. Fischer, Ruth A. Fischer The MayaTech CorporationSilver Spring, Md Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence Bergner Lawrence Bergner *Affiliations of authors: Community Oncology and Rehabilitation BranchNational Opinion Research CenterWashington, D.C. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 16, 17 August 1994, Pages 1202–1208, https://doi.org/10.1093/jnci/86.16.1202 Published: 17 August 1994 Article history Received: 10 January 1994 Revision received: 26 May 1994 Accepted: 01 June 1994 Published: 17 August 1994