tbuckley/cabot-search huggingface dataset:
Factors Affecting Anaerobic Glycolysis in Mouse and Rat Liver and in Morris Rat Hepatomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Mark Woods, Dean Burk, Jehu Hunter
Journal: JNCI Journal of the National Cancer Institute (1968)

Anaerobic glycolysis, in cells of mouse or rat liver and the Morris series of rat hepatomas, consists of a glucolytic component and a glycogenolytic component. Under anaerobic conditions both components become strongly inhibited as a result of DPNH2 (reduced form of DPN) accumulation from nonglycolytic reduction of diphosphopyridine nucleotide (DPN) in hepatic tissues. Thus the real glycolytic potential of the cells becomes rapidly masked. Additions of DPN, triphosphopyridine nucleotide (TPN), or pyruvate temporarily relieve the glycolytic inhibition by increasing the DPN/DPNH2 ratio. This paper presents detailed information concerning differential responses of glucolysis and glycogenolysis to additions of DPN4, TPN, pyruvate, 2-deoxyglucose, Δ1-testololactone, and insulin in mouse or rat livers, in a spectrum of rat hepatomas, and in certain nonhepatic tumors for comparison. In the liver-hepatoma spectrum glucolysis increases and glycogenolysis decreases, with increasing malignant growth capacity. The data reported have a bearing on the problem of localization of glycolytic activities within intact cells, and further support the Warburg concept that an increased glucolytic capacity and enhanced capacity for anaerobiosis are basic to malignant transformation. The in vitro results show that cells of liver and of hepatomas of very diverse growth rates follow the same phenomena of insulin: anti-insulin behavior, as do other tested mammalian tissues and malignant spectra derived therefrom.
Pulmonary haemodynamics of the yak, cattle, and cross breeds at high altitude.
Authors: I S Anand, E Harris, R Ferrari, P Pearce, P Harris
Journal: Thorax (1986)

The pulmonary arterial pressure of Ladakhi yaks, at an altitude of about 4500m, was not significantly different from that found in yaks bred at low altitude. The pulmonary arterial resistance, however, was slightly but significantly increased in the high altitude group. It is concluded that the yak has adapted genetically to high altitude by largely eliminating the hypoxic pulmonary vasoconstrictor response. The pulmonary arterial pressure and resistance were significantly higher in indigenous Himalayan cattle than in the yaks. The dzo (cow X yak) had pulmonary haemodynamics similar to those of the yak. Half of the stols (dzo X bull) had pulmonary haemodynamics similar to those of the yak, while in the other half the findings resembled those in the cow. The results suggest that the genetic attenuation of the hypoxic vasoconstrictor response is transmitted as a simple autosomal dominant.
Balloon-induced right ventricular outflow obstruction: a new approach to control of acute interventricular shunting after myocardial infarction in canines and swine.
Authors: J D Babb, J A Waldhausen, R Zelis
Journal: Circulation Research (1977)

Current management of ventricular septal defect (VSD) after myocardial infarction (MI) is aimed at improving left ventricular (LV) performance by afterload reduction as a means of hemodynamic stabilization or shunt control. The current investigation was undertaken to determine whether primary manipulation of right venticular (RV) performance by afterload enhancement was an effective means of reducing MI-VSD shunting. In five open-chest dogs an external LV-RV shunt was created with pulmonary-systemic flow ratios (Qp/Qs) averaging 2.26:1. Inflation of a balloon-tipped catheter in the main pulmonary artery (PA) reduced average QP/Qs to 1.28:1 and shunt flow from 783 to 343 ml/min. However, this increase in RV afterload caused further significant increases in RV systolic and end-diastolic pressure and suggested that deterioration of RV function might be limiting the usefulness of this technique. To investigate whether inotropic support for the RV would overcome this limitation, a similar shunt was created in 11 open-chest swine. We then investigated the effects of dopamine, infused at 24, 60, and 120 mug/min, on QP/QS and other hemodynamic variables both with and without PA balloon inflation. Optimal shunt control was obtained when effects of dopamine were added to those of PA balloon inflation. Shunt flow that had been 1,633 ml/min was reduced to 892 ml/min with the PA balloon and reduced further to 757 ml/min with dopamine, which also lowered RV and LV end-diastolic pressure and reduced total systemic vascular resistance. In four other swine with left anterior descending ligations, PA balloon inflation and dopamine infusion again favorably affected hemodynamics. Epicardial mapping in these swine showed an increase in S-T segment displacement, suggesting that the cumulative effect of these interventions allowed hemodynamic improvement at the expense of enhanced ischemic injury. These data indicate that acute RV outflow obstruction with a balloon catheter is an effective means of temporarily reducing acute ventricular shunting and that dopamine may be a useful pharmacological agent to use with RV afterload manipulation to stabilize a patient prior to transfer to a medical center for more definitive therapy.
Comparative Multi-Epitope-Ligand-Cartography reveals essential immunological alterations in Barrett's metaplasia and esophageal adenocarcinoma
Authors: Uta Berndt, Lars Philipsen, Sebastian Bartsch, Yuqin Hu, Christoph Röcken, Wiedenmann Bertram, Marcus Hämmerle, Thomas Rösch, Andreas Sturm
Journal: Molecular Cancer (2010)

Barrett's esophagus (BE) is caused by gastroesophageal reflux with consecutive mucosal inflammation, predisposing patients to the development of esophageal adenocarcinoma (EAC). We investigated changes in T cell-related mucosal combinatorial molecular protein patterns in both diseases using the novel Multi-Epitope-Ligand-Cartography, a unique robotic whole-cell imaging technology that simultaneously visualizes dozens of proteins in structurally intact tissues and correlates cellular localization of proteins with function. Biopsies were taken during endoscopy from BE, EAC, and normal control tissue, and proteomic microscopy was performed on 32 different epitopes. When the significance level was set to p < 0.0005 and the search depth to five antibody combinations, controls and BE can be differentiated by 63, controls and EAC by 3222, and BE from EAC by 1521 distinct protein combinations. For example, the number of activated apoptotic naïve and memory T cells was significantly increased only in BE, whereas the number of activated apoptotic helper and regulatory T cells was significantly elevated in BE and EAC. In contrast, the number of activated apoptotic cytotoxic T cells was significantly elevated only in EAC. Confirming different pathways in BE and EAC, the number of T lymphocytes with p53 expression and downregulation of bcl2 expression (CD3+p53+Bcl2-NfkB-) was significantly increased in EAC compared to BE and controls. Interestingly, the number of precursor T cells (CD7+) was significantly elevated only in EAC. These cells lack Bax and caspase-8, suggesting impaired apoptosis in the early stages of T cell differentiation. Proteomic analysis showed for the first time that proteins, which are critically involved in the mucosal immune system of the esophagus, are distinctly expressed in BE and EAC, whereas others are comparably altered in both diseases, suggesting that many pathogenic events might be shared by both diseases. Topological proteomic analysis, therefore, helps us to understand the different pathogenic events in the underlying disease pathways.
High-Frequency Oscillation for Acute Respiratory Distress Syndrome
Authors: Duncan Young, Sarah E. Lamb, Sanjoy Shah, Iain MacKenzie, William Tunnicliffe, Ranjit Lall, Kathy Rowan, Brian H. Cuthbertson
Journal: New England Journal of Medicine (2013)

Patients with the acute respiratory distress syndrome (ARDS) require mechanical ventilation to maintain arterial oxygenation, but this treatment may produce secondary lung injury. High-frequency oscillatory ventilation (HFOV) may reduce this secondary damage.In a multicenter study, we randomly assigned adults requiring mechanical ventilation for ARDS to undergo either HFOV with a Novalung R100 ventilator (Metran) or usual ventilatory care. All the patients had a ratio of the partial pressure of arterial oxygen (PaO) to the fraction of inspired oxygen (FiO) of 200 mm Hg (26.7 kPa) or less and an expected duration of ventilation of at least 2 days. The primary outcome was all-cause mortality 30 days after randomization.There was no significant between-group difference in the primary outcome, which occurred in 166 of 398 patients (41.7%) in the HFOV group and 163 of 397 patients (41.1%) in the conventional-ventilation group (P=0.85 by the chi-square test). After adjustment for study center, sex, score on the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the initial PaO:FiO ratio, the odds ratio for survival in the conventional-ventilation group was 1.03 (95% confidence interval, 0.75 to 1.40; P=0.87 by logistic regression).The use of HFOV had no significant effect on 30-day mortality in patients undergoing mechanical ventilation for ARDS. (Funded by the National Institute for Health Research Health Technology Assessment Programme; OSCAR Current Controlled Trials number, ISRCTN10416500.).
Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin
Authors: P.J. Mulholland, D.R. Ferry, D. Anderson, S.A. Hussain, A.M. Young, J.E. Cook, E. Hodgkin, L.W. Seymour, D.J. Kerr
Journal: Annals of Oncology (2001)
Inflammation and the Incidence of Type 2 Diabetes
Authors: Alain G. Bertoni, Gregory L. Burke, James A. Owusu, Mercedes R. Carnethon, Dhananjay Vaidya, R. Graham Barr, Nancy S. Jenny, Pamela Ouyang, Jerome I. Rotter
Journal: Diabetes Care (2010)

Many studies have documented associations between inflammation and type 2 diabetes incidence. We assessed potential variability in this association in the major U.S. racial/ethnic groups.
Nuclear and cytoplasmic LIMK1 enhances human breast cancer progression
Authors: Brice V McConnell, Karen Koto, Arthur Gutierrez-Hartmann
Journal: Molecular Cancer (2011)

Abstract Background LIM kinase 1 (LIMK1) is expressed in both cytoplasmic and nuclear compartments, and is a key regulator of cytoskeletal organization involved in cell migration and proliferation. LIMK1 levels are increased in several human cancers, with LIMK1 over-expression in prostate and breast cancer cells leading to tumor progression. While it has been presumed that the mechanism by which LIMK1 promotes cancer progression is via its cytoplasmic effects, the role of nuclear vs cytoplasmic LIMK1 in the tumorigenic process has not been examined. Results To determine if cytoplasmic or nuclear LIMK1 expression correlated with breast cancer, we performed immunohistochemical (IHC) analysis of breast tissue microarrays (TMAs), The IHC analysis of breast TMAs revealed that 76% of malignant breast tissue samples strongly expressed LIMK1 in the cytoplasm, with 52% of these specimens also expressing nuclear LIMK1. Only 48% of benign breast samples displayed strong cytoplasmic LIMK1 expression and 27% of these expressed nuclear LIMK1. To investigate the respective roles of cytoplamsic and nuclear LIMK1 in breast cancer progression, we targeted GFP-LIMK1 to cytoplasmic and nuclear subcellular compartments by fusing nuclear export signals (NESs) or nuclear localization sequences (NLS), respectively, to the amino-terminus of GFP-LIMK1. Stable pools of MDA-MB-231 cells were generated by retroviral transduction, and fluorescence microscopy revealed that GFP alone (control) and GFP-LIMK1 were each expressed in both the cytoplasm and nucleus of MDA-MB-231 cells, whereas NLS-GFP-LIMK1 was expressed in the nucleus and NES-GFP-LIMK1 was expressed in the cytoplasm. Western blot analyses revealed equal expression of GFP-LIMK1 and NES-GFP-LIMK1, with NLS-GFP-LIMK1 expression being less but equal to endogenous LIMK1. Also, Western blotting revealed increased levels of phospho-cofilin, phospho-FAK, phospho-paxillin, phospho-Src, phospho-AKT, and phospho-Erk1/2 in cells expressing all GFP-LIMK1 fusions, compared to GFP alone. Invasion assays revealed that all GFP-LIMK1 fusions increased MDA-MB-231 cell invasion ~1.5-fold, compared to GFP-only control cells. Tumor xenograft studies in nude mice revealed that MDA-MB-231 cells stably expressing GFP-LIMK, NLS-GFP-LIMK1 and NES-GFP-LIMK1 enhanced tumor growth 2.5-, 1.6- and 4.7-fold, respectively, compared to GFP-alone. Conclusion Taken together, these data demonstrate that LIMK1 activity in both the cytoplasmic and nuclear compartments promotes breast cancer progression, underscoring that nuclear LIMK1 contributes to the transforming function of LIMK1.
Does abciximab and stenting improve outcomes in elderly patients undergoing primary PCI for acute myocardial infarction: data from the CADILLAC trial
Authors: Giulio Guagliumi, David A. Cox, Cindy Grines, Eulogio Garcia, Thomas Stuckey, James Tcheng, John Pasquini, John Carroll, Alexandra Lansky, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2002)
Phase I and Pharmacokinetic Study of Genexol-PM, a Cremophor-Free, Polymeric Micelle-Formulated Paclitaxel, in Patients with Advanced Malignancies
Authors: Tae-You Kim, Dong-Wan Kim, Jae-Yong Chung, Sang Goo Shin, Sung-Chul Kim, Dae Seog Heo, Noe Kyeong Kim, Yung-Jue Bang
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The rationale for developing an alternative paclitaxel formulation concerns Cremophor EL-related side effects, and a novel paclitaxel delivery system might augment its therapeutic efficacy. Genexol-PM is a polymeric micelle formulated paclitaxel free of Cremophor EL. A phase I study was performed to determine the maximum tolerated dosage, dose-limiting toxicities, and the pharmacokinetic profile of Genexol-PM in patients with advanced, refractory malignancies. Experimental Design: Twenty-one patients were entered into the study. Genexol-PM was i.v. administered over 3 h every 3 weeks without premedication. The Genexol-PM dose was escalated from 135 mg/m2 to 390 mg/m2. Results: All of the patients were evaluable for toxicity and response. Acute hypersensitivity reactions were not observed. Neuropathy and myalgia were the most common toxicities. During cycle 1, grade 3 myalgia occurred in 1 patient at 230 and 300 mg/m2, respectively. At 390 mg/m2, 2 of 3 patients developed grade 4 neutropenia or grade 3 polyneuropathy. Therefore, the maximum tolerated dosage was determined to be 390 mg/m2. There were 3 partial responses (14%) among the 21 patients. Of the 3 responders, 2 were refractory to prior taxane therapy. The paclitaxel area under the curve from time 0 to infinity and peak or maximum paclitaxel concentration seemed to increase with escalating dose, except at 230 mg/m2, which suggests that Genexol-PM has linear pharmacokinetics. Conclusion: The main dose-limiting toxicities were neuropathy, myalgia, and neutropenia, and the recommended dosage for a phase II study is 300 mg/m2. Genexol-PM is believed to be superior to conventional paclitaxel in terms of the obviation of premedication and the delivery of higher paclitaxel doses without additional toxicity.
The immunogenicity of anti-TNF therapy in immune-mediated inflammatory diseases: a systematic review of the literature with a meta-analysis
Authors: Sandra Garcês, Jocelyne Demengeot, Elizabeth Benito-Garcia
Journal: Annals of the Rheumatic Diseases (2012)

Background Immunogenicity of aTNFs is one of the mechanisms behind treatment failure. Objective To assess the effect of anti-drug antibodies (ADA) on drug response to infliximab, adalimumab and etanercept, and the effect of immunosuppression on ADA detection, in patients with Rheumatoid Arthritis, Spondyloarthritis, Psoriasis and Inflammatory Bowel Diseases. Data sources PubMed, EMBASE, Cochrane databases, article reference lists (through August 19 2012). Study selection Out of 2082 studies, 17 were used in the meta-analysis (1RCT; 16 observational studies). Data extraction Two reviewers extracted data. Risk ratios (RR), 95% CI, using random-effect models, sensitivity analysis, meta-regressions and Egger's test were calculated. Data synthesis Of 865 patients, ADA against infliximab or adalimumab reduced drug response rate by 68% (RR=0.68, 95% CI=0.12 to 0.36), an effect attenuated by concomitant methotrexate (MTX): &lt;74% MTX+: RR=0.23, 95% CI=0.15 to 0.36; ≥74% MTX+: RR=0.32, 95% CI=0.22 to 0.48. Anti-etanercept antibodies were not detected. Of 936 patients, concomitant MTX or azathioprine/mercaptopurine reduced ADA frequency by 47% (RR=0.53, 95% CI=0.42 to 0.67), particularly when ADA were assessed by RIA (RR=0.36, 95% CI=0.23 to 0.55) compared with ELISA (RR=0.63, 95% CI=0.53 to 0.74). Conclusions ADA reduces drug response, an effect that can be attenuated by concomitant immunosuppression, which reduces ADA frequency. Drug immunogenicity should be considered for the management of patients receiving biological therapies.
Aurora Kinase A Inhibition Leads to p73-Dependent Apoptosis in p53-Deficient Cancer Cells
Authors: Altaf A. Dar, Abbes Belkhiri, Jeffrey Ecsedy, Alexander Zaika, Wael El-Rifai
Journal: Cancer Research (2008)

Abstract We investigated the role of Aurora kinase A (AURKA) in regulating p73-dependent apoptosis using the p53-deficient cancer cell lines H1299, TE7, and HCT116p53−/−. Overexpression of AURKA led to down-regulation of the TAp73-induced activation of the p53/p73-dependent luciferase reporter plasmid (pG13-luc). The reduction in the TAp73 transcription activity was confirmed by measuring the activity of luciferase reporters for p21/WAF1, and PUMA. The siRNA knockdown of endogenous AURKA reversed these effects and Western blot analysis showed a significant increase in the protein level of TAp73 and its downstream transcription targets, PUMA, NOXA, and p21/WAF1. The coexpression of AURKA together with TAp73 inhibited the activation of the pG13-luc, PUMA-luc, and p21/WAF1-luc reporter plasmids with reduction in the protein levels of TAp73 transcription targets. Treatment with AURKA-selective small molecule inhibitor MLN8054 led to a significant increase in the activities of pG13-luc, PUMA-luc, and p21/WAF1-luc reporter plasmids. This effect was accompanied by a significant increase in the mRNA and protein levels of several TAp73 transcription targets: p21/WAF1, PUMA, and NOXA. Flow cytometry cell cycle analysis, after MLN8054 treatment, showed more than a 2-fold increase in cell death. The apoptotic outcome was corroborated by showing an increase in cleaved caspase-3 protein levels by Western blot. Using terminal deoxynucleotidyl-transferase–mediated dUTP nick-end labeling assay, we showed that the expression of dominant-negative mutant TAp73 expression plasmid (p73DD) counteracted the MLN8054-induced cell death. Taken together, our results indicate that AURKA regulates TAp73-dependent apoptosis and highlight the potential of the AURKA inhibitor MLN8054 in treating cancers that are defective in p53 signaling. [Cancer Res 2008;68(21):8998–9004]
Are we understanding the respiratory effects of traffic related airborne particles?
Authors: F. Forastiere, A. Faustini
Journal: Thorax (2008)

There is convincing scientific evidence showing that ambient particulate matter (PM) is related to both short and long term health effects. Increased mortality and hospitalisation for cardiopulmonary causes have been noted in several studies evaluating the effects of PM10 or PM2.5 (PM <10 or 2.5 μm in diameter).1 However, urban air pollution consists of a complex mixture of gases and particulate agents that vary over time and through space, depending on its sources, distance and meteorological conditions.2 Much of the scientific interest has been devoted to the toxicology of the ultrafine fraction of airborne particles (<0.1 μm).3 These particles are usually emitted from combustion sources (eg, gasoline or diesel powered engines) or are formed from chemical conversion of gases in the atmosphere. They are relatively short lived and combine into larger particles between 0.1 and about 1 μm in diameter (accumulation mode). These particles tend to penetrate deeper in the alveolar part of the lung and have a larger surface area than larger sized particles, eliciting greater potential interaction with human tissues and a stronger inflammatory reaction. The epidemiological evidence linking ultrafine particles with respiratory health effects is still limited and controversial. In the current issue of Thorax , Halonen and colleagues4 provide new and compelling evidence on the respiratory effects of particles of various sizes that will certainly stimulate further research (see page 635) .

Different sized particles were measured daily in Helsinki over a period of 7 years, and a source apportionment method was applied to separate the PM2.5 fraction from four sources (traffic, long range transport, soil and road dust, and coal/oil combustion). …
An Unusual Case of Cutaneous Diphtheria
Authors: Max Bader
Journal: JAMA (1978)

SEATTLE-KING County has experienced an outbreak of diphtheria since 1972.<sup>1</sup>It has been characterized mainly by cutaneous diphtheria among alcohol-using indigent adults in Seattle's Skid Road area. During this period, 749 cases and carriers of diphtheria were identified, and one, described here, was an unusual case of chronic intermittent cutaneous diphtheria. <h3>Methods</h3> For three years the patient was often seen at one of five health facilities: Harborview Medical Center (HMC), Seattle-King County Health Department Communicable Disease Control Clinic, Seattle City Jail, Seattle Indian Health Clinic, and Pioneer Square Neighborhood Health Center. There, the patient's skin lesions were swabbed with a sterile cotton-tipped applicator, and the material was either directly inoculated onto blood agar, tellurite, and Loeffler's blood culture media, or, in several of the facilities, Amies transport medium without charcoal was used initially. Nasopharyngeal and throat cultures were also obtained when the patient was examined at the Health Department.
Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial
Authors: Manfred Schmidt, Salima Hacein-Bey-Abina, Manuela Wissler, Frederique Carlier, Annick Lim, Claudia Prinz, Hanno Glimm, Isabelle Andre-Schmutz, Christophe Hue, Alexandrine Garrigue, Francoise Le Deist, Chantal Lagresle, Alain Fischer, Marina Cavazzana-Calvo, Christof von Kalle
Journal: Blood (2004)