tbuckley/cabot-search huggingface dataset:
Stage, Age, Comorbidity, and Direct Costs of Colon, Prostate, and Breast Cancer Care
Authors: S H Taplin, W Barlow, N Urban, M T Mandelson, D J Timlin, L Ichikawa, P Nefcy
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Stage, Age, Comorbidity, and Direct Costs of Colon, Prostate, and Breast Cancer Care Get access Stephen H. Taplin, Stephen H. Taplin Search for other works by this author on: Oxford Academic PubMed Google Scholar William Barlow, William Barlow Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicole Urban, Nicole Urban Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret T. Mandelson, Margaret T. Mandelson Search for other works by this author on: Oxford Academic PubMed Google Scholar Deborah J. Timlin, Deborah J. Timlin Search for other works by this author on: Oxford Academic PubMed Google Scholar Laura Ichikawa, Laura Ichikawa Search for other works by this author on: Oxford Academic PubMed Google Scholar Pauline Nefcy Pauline Nefcy Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 6, 15 March 1995, Pages 417–426, https://doi.org/10.1093/jnci/87.6.417 Published: 15 March 1995 Article history Received: 03 August 1994 Revision received: 07 December 1994 Accepted: 29 December 1994 Published: 15 March 1995
Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM
Authors: Rolf A. Brekken, Pauli Puolakkainen, David C. Graves, Gail Workman, Sharon R. Lubkin, E. Helene Sage
Journal: Journal of Clinical Investigation (2003)

SPARC, a 32-kDa glycoprotein, participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions. Major functions defined for SPARC in vitro are de-adhesion and antiproliferation. In vivo, SPARC is restricted in its expression to remodeling tissues, including pathologies such as cancer. However, the function of endogenous SPARC in tumor growth and progression is not known. Here, we report that implanted tumors grew more rapidly in mice lacking SPARC. We observed that tumors grown in SPARC null mice showed alterations in the production and organization of ECM components and a decrease in the infiltration of macrophages. However, there was no change in the levels of angiogenic growth factors in comparison to tumors grown in wild-type mice, although there was a statistically significant difference in total vascular area. Whereas SPARC did inhibit the growth of tumor cells in vitro, it did not have a demonstrable effect on the proliferation or apoptosis of tumor cells in vivo. These data indicate that host-derived SPARC is important for the appropriate organization of the ECM in response to implanted tumors and highlight the importance of the ECM in regulating tumor growth.
A Computed Tomographic Scan Assessment of Endotracheal Suctioning-Induced Bronchoconstriction in Ventilated Sheep
Authors: QIN LU, ANDRE CAPDEROU, PHILIPPE CLUZEL, ERIC MOURGEON, LAMINE ABDENNOUR, JEAN-DOMINIQUE LAW-KOUNE, CHRISTIAN STRAUS, PHILIPPE GRENIER, MARC ZELTER, JEAN-JACQUES ROUBY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

This study was directed at assessing changes in bronchial cross-sectional surface areas (BCSA) and in respiratory resistance induced by endotracheal suctioning in nine anesthetized sheep. Cardiorespiratory parameters (Swan–Ganz catheter), respiratory resistance (inspiratory occlusion technique), BCSA, and lung aeration (computed tomography) were studied at baseline, during endotracheal suctioning, and after 20 consecutive hyperinflations. Measurements performed initially at an inspired oxygen fraction (Fi O2 ) of 0.3 were repeated at an Fi O2 of 1.0. At an Fi O2 of 0.3, endotracheal suctioning resulted in atelectasis, a reduction in BCSA of 29 ± 23% (mean ± SD), a decrease in arterial oxygen saturation from 95 ± 3% to 87 ± 12% (p = 0.02), an increase in venous admixture from 19 ± 10% to 31 ± 19% (p = 0.006), and an increase in lung tissue resistance (DRrs) (p = 0.0003). At an Fi O2 of 1.0, despite an extension of atelectasis and an increase in pulmonary shunt from 19 ± 5% to 36 ± 2% (p < 0.0001), arterial O2 desaturation was prevented and BCSA decreased by only 7 ± 32%. A recruitment maneuver after endotracheal suctioning entirely reversed the suctioning-induced increase in DRrs and atelectasis. In three lidocaine-pretreated sheep, the endotracheal suctioning-induced reduction of BCSA was entirely prevented. These data suggest that the endotracheal suctioning-induced decrease in BCSA is related to atelectasis and bronchoconstriction. Both effects can be reversed by hyperoxygenation maneuver before suctioning in combination with recruitment maneuver after suctioning.
Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy
Authors: Eva Untersmayr, Helle Vestergaard, Hans-Jørgen Malling, Louise Bjerremann Jensen, Michael H. Platzer, George Boltz-Nitulescu, Otto Scheiner, Per Stahl Skov, Erika Jensen-Jarolim, Lars K. Poulsen
Journal: Journal of Allergy and Clinical Immunology (2007)
Four Artificial Heart Valves
Authors: Micon Bijl, R B A van den Brink
Journal: New England Journal of Medicine (2005)

A 67-year-old woman reported having progressive shortness of breath over several months, three years after undergoing aortic-valve replacement for aortic insufficiency. The patient had migraine headaches for which she had received 2 mg of ergotamine tartrate daily for many years. On physical examination, her blood pressure was 170/95 mm Hg. She had elevated jugular venous pressure, and grade 2/6 systolic and diastolic murmurs were noted along the right sternal border. The results of laboratory analysis for 5-hydroxyindoleacetic acid were normal. Echocardiography showed a normal aortic-valve prosthesis and thickened mitral, pulmonary, and tricuspid valves with severe insufficiency. Cardiac catheterization revealed elevated . . .
Epigenetic upregulation of metabotropic glutamate receptor 2 in the spinal cord attenuates oestrogen-induced visceral hypersensitivity
Authors: Dong-Yuan Cao, Guang Bai, Yaping Ji, Richard J Traub
Journal: Gut (2014)

<h3>Objective</h3> Epigenetic mechanisms are potential targets to relieve somatic pain. However, little is known whether epigenetic regulation interferes with visceral pain. Previous studies show that oestrogen facilitates visceral pain. This study aimed to determine whether histone hyperacetylation in the spinal cord could attenuate oestrogen-facilitated visceral pain. <h3>Design</h3> The effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on the magnitude of the visceromotor response (VMR) to colorectal distention was examined in ovariectomised rats with/without oestrogen replacement. An additional interaction with the metabotropic glutamate receptor 2/3 (mGluR2/3) antagonist LY341495 was tested. The levels of acetylated histone and mGluR2 mRNA and protein were analysed. The binding of acetylated H3 and oestrogen receptor α (ERα) to the <i>GRM2</i> promoter was measured by chromatin immunoprecipitation coupled with qPCR. <h3>Results</h3> In ovariectomised rats, 17β-estradiol (E2), but not safflower oil, increased the magnitude of the VMR to colorectal distention. SAHA attenuated the E2-facilitated VMR, but had no effect in safflower oil-treated rats. Subsequent spinal administration of LY341495 reversed the antinociceptive effect of SAHA in E2 rats. In addition, SAHA increased mGluR2 mRNA and protein in the spinal dorsal horn following E2, but not vehicle, treatment. In contrast, neither E2 nor SAHA alone altered mGluR2 mRNA. SAHA increased binding of H3K9ac and ERα to the same regions of the <i>GRM2</i> promoter in E2-SAHA-treated animals. <h3>Conclusions</h3> Histone hyperacetylation in the spinal cord attenuates the pronociceptive effects of oestrogen on visceral sensitivity, suggesting that epigenetic regulation may be a potential approach to relieve visceral pain.
Additional analysis of antigen-specific Interleukin-2 release does not improve the performance of IGRAs for the differentiation of different states of mycobacterium tuberculosis infection
Authors: Dumitru Chesov, Christoph Lange, Franziska Daduna, Valeriu Crudu, Rosemarie Preyer, Martin Ernst, Barbara Kalsdorf
Journal: European Respiratory Journal (2014)

Introduction  Discrimination of tuberculosis (TB) from latent infection with  Mycobacterium tuberculosis  (LTBI) by immunodiagnostic assays remains challenging. This study compares the performance of a novel two color FluoroSpot with an established interferon-γ (IFNγ) release assay (IGRA) EliSpot. We hypothesize that additional information of Mtb-specific interleukin (IL)-2 release will improve the immunodiagnosis of different stages of Mtb-infection.   Methods  Immune responses of peripheral blood mononuclear cells were assessed using EliSpot and FluoroSpot test systems in 18 culture confirmed pulmonary TB cases, 41 healthy controls (24 - LTBI), and 10 persons with known cured TB. The number of IFNγ spot forming cells in EliSpot was compared with IFNγ in FluoroSpot, furthermore IL2 +  or IFNγ + IL2 +  producing T-cells were determined.   Results  IFNγ response in EliSpot and FluoroSpot showed a good correlation (ESAT6 r 2 =0,67; CFP10 r 2 =0,73). Against to expectations, the analysis of IL2 +  and IFNγ + IL2 +  cells did not improve differentiation between TB, LTBI and cured TB substantially. The number of single IFNγ + IL2 - producing cells was significantly higher in patients with TB compared with LTBI controls (ESAT6-induced p=0,013) as well as in patients with TB compared with former TB patients (CFP10-induced p=0,006). However a big overlap of test results hampers to distinguish between the cohorts.   Conclusion  EliSpot and FluoroSpot results correlate well with each other, however separate analysis of IL-2 and IFNγ secretion by antigen specific T-cells does not allow differentiation of TB from LTBI in clinical practice.
Optimal Medical Therapy with or without PCI for Stable Coronary Disease
Authors: William E. Boden, Robert A. O'Rourke, Koon K. Teo, Pamela M. Hartigan, David J. Maron, William J. Kostuk, Merril Knudtson, Marcin Dada, Paul Casperson, Crystal L. Harris, Bernard R. Chaitman, Leslee Shaw, Gilbert Gosselin, Shah Nawaz, Lawrence M. Title, Gerald Gau, Alvin S. Blaustein, David C. Booth, Eric R. Bates, John A. Spertus, Daniel S. Berman, G.B. John Mancini, William S. Weintraub
Journal: New England Journal of Medicine (2007)

In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov].).
The Public Health and Air Pollution in Asia (PAPA) Project: Estimating the Mortality Effects of Particulate Matter in Bangkok, Thailand
Authors: Nuntavarn Vichit-Vadakan, Nitaya Vajanapoom, Bart Ostro
Journal: Environmental Health Perspectives (2008)

Air pollution data in Bangkok, Thailand, indicate that levels of particulate matter with aerodynamic diameter < or = 10 microm (PM(10)) are significantly higher than in most cities in North America and Western Europe, where the health effects of PM(10) are well documented. However, the pollution mix, seasonality, and demographics are different from those in developed Western countries. It is important, therefore, to determine whether the large metropolitan area of Bangkok is subject to similar effects of PM(10).This study was designed to investigate the mortality risk from air pollution in Bangkok, Thailand.The study period extended from 1999 to 2003, for which the Ministry of Public Health provided the mortality data. Measures of air pollution were derived from air monitoring stations, and information on temperature and relative humidity was obtained from the weather station in central Bangkok. The statistical analysis followed the common protocol for the multicity PAPA (Public Health and Air Pollution Project in Asia) project in using a natural cubic spline model with smooths of time and weather.The excess risk for non-accidental mortality was 1.3% [95% confidence interval (CI), 0.8-1.7] per 10 microg/m(3) of PM(10), with higher excess risks for cardiovascular and above age 65 mortality of 1.9% (95% CI, 0.8-3.0) and 1.5% (95% CI, 0.9-2.1), respectively. In addition, the effects from PM(10) appear to be consistent in multipollutant models.The results suggest strong associations between several different mortality outcomes and PM(10). In many cases, the effect estimates were higher than those typically reported in Western industrialized nations.
FOXO1A Is a Target for HER2-Overexpressing Breast Tumors
Authors: Yanyuan Wu, Xiying Shang, Marianna Sarkissyan, Dennis Slamon, Jaydutt V. Vadgama
Journal: Cancer Research (2010)

Abstract Trastuzumab treatment has improved the overall survival of HER2-overexpressing breast cancer patients. However, many of these patients will eventually become resistant to treatment. The mechanisms that contribute to resistance to trastuzumab are unknown. In this study, we tested the hypothesis that targeting of the FKHR transcription factor FOXO1A in HER2-overexpressing breast tumor cells can overcome the trastuzumab resistance in vitro. We have shown that overexpression of HER2 leads to activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway and subsequent inactivation of FOXO1A in HER2-overexpressing breast cancer cells SKBR3, BT474, and MCF7-HER2. In wild-type SKBR3 and BT474 cells, trastuzumab downregulates active Akt and increases FOXO1A expression that leads to increase in p27kip1 and decrease in cyclin D1 and finally inhibits cell proliferation. In contrast, the effect of trastuzumab was eliminated by the reduction of FOXO1A in HER2-overexpressing cells with constitutively active Akt1 (SKBR3/AA28 and BT474/AA9). The downregulation of FOXO1A resulted in nuclear export of p27kip1. Blocking the constitutively active Akt by a specific Akt/protein kinase B signaling inhibitor-2 (API-2) significantly increased FOXO1A expression and rendered the cells more responsive to trastuzumab-induced growth inhibition. Reactivation of FOXO1A by stable or transient transfection also restored the growth-inhibitory effects of trastuzumab in SKBR3/AA28, BT474/AA9, and MCF7-HER2 cells. Knocking down FOXO1A by small interfering RNA resulted in reducing trastuzumab-induced growth inhibition. In summary, trastuzumab can inhibit proliferation of HER2-overexpressing breast cancer cells by reactivating FOXO1A through inhibition of the PI3K/Akt pathway. FOXO1A may therefore serve as a target for HER2-overexpressing breast tumors. Cancer Res; 70(13); 5475–85. ©2010 AACR.
The N-terminal domain of thrombomodulin sequesters high-mobility group-B1 protein, a novel antiinflammatory mechanism
Authors: Kazuhiro Abeyama, David M. Stern, Yuji Ito, Ko-ichi Kawahara, Yasushi Yoshimoto, Motoyuki Tanaka, Tomonori Uchimura, Nobuo Ida, Yoshiaki Yamazaki, Shingo Yamada, Yasuhiko Yamamoto, Hiroshi Yamamoto, Satoshi Iino, Noboru Taniguchi, Ikuro Maruyama
Journal: Journal of Clinical Investigation (2005)

Thrombomodulin (TM) is an endothelial anticoagulant cofactor that promotes thrombin-mediated formation of activated protein C (APC). We have found that the N-terminal lectin-like domain (D1) of TM has unique antiinflammatory properties. TM, via D1, binds high-mobility group-B1 DNA-binding protein (HMGB1), a factor closely associated with necrotic cell damage following its release from the nucleus, thereby preventing in vitro leukocyte activation, in vivo UV irradiation–induced cutaneous inflammation, and in vivo lipopolysaccharide-induced lethality. Our data also demonstrate antiinflammatory properties of a peptide spanning D1 of TM and suggest its therapeutic potential. These findings highlight a novel mechanism, i.e., sequestration of mediators, through which an endothelial cofactor, TM, suppresses inflammation quite distinctly from its anticoagulant cofactor activity, thereby preventing the interaction of these mediators with cell surface receptors on effector cells in the vasculature.
Microsatellite Instability Testing in Colorectal Carcinoma: Choice of Markers Affects Sensitivity of Detection of Mismatch Repair–Deficient Tumors
Authors: Stephanie B. Hatch, Harry M. Lightfoot, Christopher P. Garwacki, Dominic T. Moore, Benjamin F. Calvo, John T. Woosley, Janiece Sciarrotta, William K. Funkhouser, Rosann A. Farber
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Microsatellite instability (MSI) is found in 10% to 15% of sporadic colorectal tumors and is usually caused by defects in DNA mismatch repair (MMR). In 1997, a panel of microsatellite markers including mononucleotide and dinucleotide repeats was recommended by a National Cancer Institute workshop on MSI. We investigated the relationship between instability of these markers and MMR protein expression in a cohort of sporadic colorectal cancer patients. Experimental Design: Paraffin sections of normal and tumor tissue from 262 colorectal cancer patients were examined for MSI status by PCR amplification and for MMR protein expression using antibodies against hMLH1, hPMS2, hMSH2, and hMSH6. Results: Twenty-six (10%) of the patients studied had tumors with a high level of MSI (MSI-H). The frequencies of MSI were the same in African-American and Caucasian patients. Each of the MSI-H tumors had mutations in both mononucleotide and dinucleotide repeats and had loss of MMR protein expression, as did two tumors that had low levels of MSI (MSI-L). These two MSI-L tumors exhibited mutations in mononucleotide repeats only, whereas eight of the other nine MSI-L tumors had mutations in just a single dinucleotide repeat. There was not a statistically significant difference in outcomes between patients whose tumors were MMR-positive or MMR-negative, although there was a slight trend toward improved survival among those with MMR-deficient tumors. Conclusions: The choice of microsatellite markers is important for MSI testing. Examination of mononucleotide repeats is sufficient for detection of tumors with MMR defects, whereas instability only in dinucleotides is characteristic of MSI-L/MMR-positive tumors.
Population-specific effects of<i>SLC17A1</i>genotype on serum urate concentrations and renal excretion of uric acid during a fructose load
Authors: Nicola Dalbeth, Meaghan E House, Gregory D Gamble, Anne Horne, Lauren Purvis, Angela Stewart, Marilyn Merriman, Murray Cadzow, Amanda Phipps-Green, Tony R Merriman
Journal: Annals of the Rheumatic Diseases (2013)

Solute carrier family 17 member 1 (SLC17A1) is an anion exchanger that secretes uric acid into the urine.1 ,2 Genetic variation in SLC17A1 has been associated with hyperuricaemia and gout.3–5 The minor allele (A) of single nucleotide polymorphism (SNP) rs1183201 is associated with a reduced risk of gout in European and western Polynesian people, with a weaker (non-significant) effect in eastern Polynesian people.4 rs1183201 is a tag SNP in strong linkage disequilibrium for the possible aetiological variant ( rs1165196 ) in SLC17A1 .4

Variation in another renal uric acid transporter SLC2A9 influences serum urate (SU) and fractional excretion of uric acid (FEUA) responses to a fructose load in European, but not Polynesian participants.6 It is unknown whether other genetic factors also contribute to fructose-induced SU responses. The aim of this study was to determine the influence of SLC17A1 variation on SU and FEUA responses during a fructose load.

Healthy volunteers provided serum and urine samples immediately before and 30, 60, 120 and 180 min after ingesting a 64 g fructose solution, as previously described.6 Data were analysed based …
Anabolic androgenic steroids induce micronuclei in buccal mucosa cells of bodybuilders
Authors: O Torres-Bugarín, R Covarrubias-Bugarín, A L Zamora-Perez, B M G Torres-Mendoza, M García-Ulloa, F G Martínez-Sandoval
Journal: British Journal of Sports Medicine (2007)

To evaluate genotoxicity of anabolic androgenic steroids (AAS) in male bodybuilders by a micronucleus assay in buccal mucosa cells.11 male bodybuilders volunteered to participate in this study and two groups were formed: group 1 (n = 6), without AAS consumption and group 2 (n = 5), with AAS consumption. A sample of buccal epithelium was taken from each participant once a week for 6 weeks. Samples were fixed, stained and analysed by a light microscope, and 2000 cells were counted from each slide. Results are expressed as micronucleated cells (MNC) per 1000 cells and were analysed by the Mann-Whitney U test and Wilcoxon's test.A marked increased in MNC was seen in bodybuilders with AAS consumption compared with those without AAS consumption (mean (SD) 4.1 (2.4) MNC/1000 cells vs 0.4 (0.4) MNC/1000 cells, respectively; p<0.004). Intragroup comparisons showed no differences in the MNC frequencies during the sampling time in group 1, whereas the MNC frequency in group 2 varied significantly, reaching the highest MNC frequencies in the third and fourth week of sampling (5.9 (2.4) MNC/1000 cells; 5.8 (1.8) MNC/1000 cells, respectively); frequency in the first sampled week was 1.1 (0.1) MNC/1000 cells. Significant differences in all sampled weeks were found between the two groups.AAS consumption increased the frequency of MNC from buccal mucosa in bodybuilders.