tbuckley/cabot-search huggingface dataset:
Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart
Authors: L HEATHER, M COLE, C LYGATE, R EVANS, D STUCKEY, A MURRAY, S NEUBAUER, K CLARKE
Journal: Cardiovascular Research (2006)

Objectives: Cardiac fatty acid uptake occurs predominantly via sarcolemmal transporter proteins; fatty acid translocase (FAT/CD36), plasma membrane fatty acid binding protein (FABPpm) and fatty acid transporter proteins (FATP) 1 and 6. We hypothesised that levels of the fatty acid transporters would be reduced in the chronically infarcted rat heart, in parallel with reduced dependence on fatty acid utilisation.
Acylglycerol kinase promotes cell proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor
Authors: Xi Wang, Chuyong Lin, Xiaohui Zhao, Aibin Liu, Jinrong Zhu, Xinghua Li, Libing Song
Journal: Molecular Cancer (2014)

Acylglycerol kinase (AGK) is reported to be overexpressed in multiple cancers. The clinical significance and biological role of AGK in breast cancer, however, remain to be established. AGK expression in breast cancer cell lines, paired patient tissues were determined using immunoblotting and Real-time PCR. 203 human breast cancer tissue samples were analyzed by immunochemistry (IHC) to investigate the relationship between AGK expression and the clinicopathological features of breast cancer. Functional assays, such as colony formation, anchorage-independent growth and BrdU assay, and a xenograft tumor model were used to determine the oncogenic role of AGK in human breast cancer progression. The effect of AGK on FOXO1 transactivity was further investigated using the luciferase reporter assays, and by detection of the FOXO1 downstream genes. Herein, we report that AGK was markedly overexpressed in breast cancer cells and clinical tissues. Immunohistochemical analysis showed that the expression of AGK significantly correlated with patients' clinicopathologic characteristics, including clinical stage and tumor-nodule-metastasis (TNM) classification. Breast cancer patients with higher levels of AGK expression had shorter overall survival compared to patients with lower AGK levels. We gained valuable insights into the mechanism of AGK expression in breast cancer cells by demonstrating that overexpressing AGK significantly enhanced, whereas silencing endogenous AGK inhibited, the proliferation and tumorigenicity of breast cancer cells both in vitro and in vivo. Furthermore, overexpression of AGK enhanced G1-S phase transition in breast cancer cells, which was associated with activation of AKT, suppression of FOXO1 transactivity, downregulation of cyclin-dependent kinase inhibitors p21 Cip1 and p27 Kip1 and upregulation of the cell cycle regulator cyclin D1. Taken together, these findings provide new evidence that AGK plays an important role in promoting proliferation and tumorigenesis in human breast cancer and may serve as a novel prognostic biomarker and therapeutic target in this disease.
Distinct BRAF (V600E) and KRAS Mutations in High Microsatellite Instability Sporadic Colorectal Cancer in African Americans
Authors: Krishan Kumar, Hassan Brim, Francis Giardiello, Duane T. Smoot, Mehdi Nouraie, Edward L. Lee, Hassan Ashktorab
Journal: Clinical Cancer Research (2009)

Colorectal cancer develops through genetic, epigenetic, and environmental events that result in uncontrolled cell proliferation. Colorectal cancer incidence and mortality is higher in African Americans (AA) than in the general population. Here, we carried out a molecular analysis of sporadic colorectal cancer tumors from AAs to investigate possible explanations for the observed disparities.A total of 222 AA colorectal cancer tumors were analyzed for microsatellite instability (MSI) for protein expression of two DNA mismatch repair genes, MLH1 and MSH2, by immunohistochemistry; for the methylation silencing of MLH1, p16, APC, and APC2 promoters by methylation-specific PCR; and for point mutations in two oncogenes, KRAS and BRAF, by sequencing.In our sample, 19.8% of the AAs colorectal cancer tumors were MSI high (MSI-H) and did not associate with any of the clinicopathologic features, except tumor differentiation. Higher levels of inactive DNA mismatch repair proteins MLH1 (41%) and MSH2 (33%) were found by immunohistochemistry. Methylation-specific PCR analysis revealed a high level of methylation for MLH1 (66%), APC (53%), and APC2 (90%), but not for p16 (26%). BRAF mutations were only within the MSI-H tumors, whereas most (64%) of KRAS mutations were found within the non-MSI-H group.MLH1, MSH2, and BRAF alterations are significantly associated with MSI-H phenotype, unlike APC, APC2 and KRAS alterations. The prominent role of DNA mismatch repair gene suppression in MSI-H and a distinctive role of BRAF and KRAS mutations with respect to MSI status are supported by this study.
Computer-Assisted Delivery of Cognitive-Behavioral Therapy for Addiction: A Randomized Trial of CBT4CBT
Authors: Kathleen M. Carroll, Samuel A. Ball, Steve Martino, Charla Nich, Theresa A. Babuscio, Kathryn F. Nuro, Melissa A. Gordon, Galina A. Portnoy, Bruce J. Rounsaville
Journal: American Journal of Psychiatry (2008)

Objectives: This study evaluated the efficacy of a computer-based version of cognitive-behavioral therapy (CBT) for substance dependence. Method: This was a randomized clinical trial in which 77 individuals seeking treatment for substance dependence at an outpatient community setting were randomly assigned to standard treatment or standard treatment with biweekly access to computer-based training in CBT (CBT4CBT) skills. Results: Treatment retention and data availability were comparable across the treatment conditions. Participants assigned to the CBT4CBT condition submitted significantly more urine specimens that were negative for any type of drugs and tended to have longer continuous periods of abstinence during treatment. The CBT4CBT program was positively evaluated by participants. In the CBT4CBT condition, outcome was more strongly associated with treatment engagement than in treatment as usual; furthermore, completion of homework assignments in CBT4CBT was significantly correlated with outcome and a significant predictor of treatment involvement. Conclusions: These data suggest that CBT4CBT is an effective adjunct to standard outpatient treatment for substance dependence and may provide an important means of making CBT, an empirically validated treatment, more broadly available.
Lipopolysaccharide antagonists block taxol-induced signaling in murine macrophages.
Authors: C L Manthey, N Qureshi, P L Stütz, S N Vogel
Journal: The Journal of Experimental Medicine (1993)

Taxol is the prototype of a new class of microtubule stabilizing agents with promising anticancer activity. Several studies show that taxol mimics the actions of lipopolysaccharide (LPS) on murine macrophages. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) and SDZ 880.431 to block taxol-induced effects. RsDPLA and SDZ 880.431 are lipid A analogues that lack LPS-like activity, but inhibit the actions of LPS, presumably by blocking critical cellular binding sites. We report that RsDPLA and SDZ 880.431 potently inhibited taxol-induced TNF secretion, gene activation, and protein-tyrosine phosphorylation. The role of microtubules in taxol signaling was investigated. Taxol-induced microtubule bundling in primary and transformed RAW 264.7 macrophages was not blocked by RsDPLA or SDZ 880.431. Taxotere, a semisynthetic taxoid, was more potent than taxol as an inducer of microtubule bundling, but did not induce tumor necrosis factor alpha secretion and gene activation. These data dissociate the microtubule effects of taxol from macrophage stimulation and suggest that taxol stimulates macrophages through an LPS receptor-dependent mechanism. The results underscore the potential of taxol as a tool for studying LPS receptor activation and provide insights into possible therapeutic actions of this new class of drugs.
Measurement of inflammatory markers in the breath condensate of children with cystic fibrosis
Authors: S. Cunningham, J.R. McColm, L Pei Ho, A.P Greening, T.G Marshall
Journal: European Respiratory Journal (2000)

Identifying noninvasive markers of pulmonary inflammation would be useful in assessing new therapies in children. Breath condensate is a simple and potentially acceptable sample medium even in small children. The technique has previously been used in adults, but not children with cystic fibrosis. The technique was assessed in 36 children with cystic fibrosis (mean age 10.4 yrs) and 17 control subjects, analysing samples for nitrite, interleukin(IL)-8 and salivary and nasal contamination. Correlations were made between levels of the inflammatory markers and forced expiratory volume in one second/forced vital capacity, chest radiograph score and use of inhaled steroids. On samples without significant contamination (<10 u x L(-1) amylase) nitrite was detected in 93% of samples at a median concentration of 3.0 microM compared with 50% of control samples at a median of 0.5 microM. Condensate amylase levels did not correlate with the nitrite value obtained (r=0.31). IL-8 was detected in 33% of CF samples. Breath condensate is an acceptable method of sample collection in children. Nitrite was raised in breath condensate from patients with cystic fibrosis when compared with control subjects.
Clinical efficacy of integrilin in unstable angina is accompanied by a modest increase in hemorrhagic risk: the PURSUIT trial
Authors: A.M. Lincoff, R.A. Harrington, R.M. Califf, L.G. Berdan, M.M. Kitt, B.D. Weatherly, N.S. Kleiman, E.J. Topol
Journal: Journal of the American College of Cardiology (1998)
Increased Carotid Intima-Media Thickness as a Predictor of the Presence and Extent of Abnormal Myocardial Perfusion in Type 2 Diabetes
Authors: Roxana Djaberi, Joanne D. Schuijf, J. Wouter Jukema, Ton J. Rabelink, Marcel P. Stokkel, Jan W. Smit, Eelco J. de Koning, Jeroen J. Bax
Journal: Diabetes Care (2009)

OBJECTIVE Identification of asymptomatic patients with type 2 diabetes at increased risk for coronary artery disease (CAD) remains a challenge. We evaluated the potential of carotid intima-media thickness (CIMT) for prediction of abnormal myocardial perfusion in this population. RESEARCH DESIGN AND METHODS CIMT and SPECT myocardial perfusion imaging were assessed in 98 asymptomatic patients with type 2 diabetes. An increased CIMT was defined as ≥75th percentile of reference values. RESULTS Increased CIMT was an independent predictor of the extent of abnormal perfusion (P &amp;lt; 0.001). In patients with increased CIMT as compared with patients with normal CIMT, abnormal perfusion (75 vs. 9%) and severely abnormal perfusion (28 vs. 3%) were observed more frequently. CONCLUSIONS Increased CIMT was significantly related to the presence and extent of abnormal myocardial perfusion. Assessment of CIMT may be useful to identify asymptomatic patients with type 2 diabetes at higher risk for CAD.
A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June-July 2009
Authors: U C de Silva, J Warachit, S Waicharoen, M Chittaganpitch
Journal: Eurosurveillance (2009)

As the influenza A(H1N1)v pandemic unfolds globally, it is vital to monitor closely for signals of change in the current patterns of transmission. We estimate the basic reproduction ratio for A(H1N1)v virus in Thailand and propose a method to keep track of the actual case count notwithstanding the exponential growth rate.
B Cell–Activating Factor. An Orchestrator of Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease
Authors: Francesca Polverino, Borja G. Cosio, Jaime Pons, Maria Laucho-Contreras, Paula Tejera, Amanda Iglesias, Angel Rios, Andreas Jahn, Jaume Sauleda, Miguel Divo, Victor Pinto-Plata, Lynette Sholl, Ivan O. Rosas, Alvar Agustí, Bartolome R. Celli, Caroline A. Owen
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Patients with chronic obstructive pulmonary disease (COPD) have increased pulmonary lymphoid follicle (LF) counts. B cell-activating factor of tumor necrosis factor family (BAFF) regulates B cells in health, but its role in COPD pathogenesis is unclear.To determine whether BAFF expression in pulmonary LFs correlates with COPD severity, LF size or number, and/or readouts of B-cell function in LFs.We correlated BAFF immunostaining in LFs in lung explants or biopsies from nonsmoking control subjects (NSC), smokers without COPD (SC), and patients with COPD with the number and size of LFs, and LF B-cell apoptosis, activation, and proliferation. We analyzed serum BAFF levels and BAFF expression in B cells in blood and bronchoalveolar lavage samples from the same subject groups. We assessed whether: (1) cigarette smoke extract (CSE) increases B-cell BAFF expression and (2) recombinant BAFF (rBAFF) rescues B cells from CSE-induced apoptosis by inhibiting activation of nuclear factor-κB (NF-κB).Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD had increased numbers and larger pulmonary LFs than patients with GOLD stages I-II COPD and SC. We identified two main types of pulmonary LFs: (1) type A, the predominant type in GOLD stages I-II COPD and SC, characterized by abundant apoptotic but few BAFF-positive cells (mostly B cells); and (2) type B, the main type in GOLD stage IV COPD, characterized by abundant BAFF-positive cells but few apoptotic cells (mostly B cells). BAFF levels were also higher in blood and bronchoalveolar lavage B cells in patients with COPD versus NSC and SC. Surprisingly, rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CSE-induced NF-κB activation.Our data support the hypothesis that B-cell BAFF expression creates a self-perpetuating loop contributing to COPD progression by promoting pulmonary B-cell survival and LF expansion.
High Levels of Multiple Wolbachia Infection and Recombination in the Ant Formica exsecta
Authors: M. Reuter
Journal: Molecular Biology and Evolution (2003)

Wolbachia bacteria are intracellular symbionts of many arthropod species. Their spread through host populations is promoted by drastic alterations imposed on their hosts' reproductive physiology. In the present study, we analyzed the association between Wolbachia strains and host mitochondrial haplotypes in a Swiss population of the ant Formica exsecta. In this species, female dispersal is extremely limited and the mitochondrial haplotypes are strongly differentiated between and within subpopulations. Our study revealed exceptionally high levels of multiple infection, with all ants harboring four or five distinct Wolbachia strains. Four of these strains were present in all ants analyzed. A fifth strain was associated with only three of the five mitochondrial haplotypes. An analysis of the Wolbachia gene wsp further revealed an unexpected high rate of recombination, with three of the five Wolbachia strains appearing to have arisen by homologous recombination.
The Biocompatibility of Nanodiamonds and Their Application in Drug Delivery Systems
Authors: Ying Zhu, Jing Li, Wenxin Li, Yu Zhang, Xiafeng Yang, Nan Chen, Yanhong Sun, Yun Zhao, Chunhai Fan, Qing Huang
Journal: Theranostics (2012)

Nanodiamonds (NDs), as a new member of the carbon nanoparticles family, have attracted more and more attention in biomedicine recently due to their excellent physical and chemical properties. This paper summarizes the main results from the in vitro and in vivo safety assessments of NDs and reports the application of NDs in the development of drug delivery systems. In view of the NDs' characteristics of easy formation of a porous cluster structure in solution, an adsorption model for a variety of functional molecules on the ND clusters is proposed, which provides new ideas for developing a novel smart drug with various features such as sustained-release, targeting, and fluorescence imaging.
Natriuretic Peptide–driven Fluid Management during Ventilator Weaning
Authors: Armand Mekontso Dessap, Ferran Roche-Campo, Achille Kouatchet, Vinko Tomicic, Gaetan Beduneau, Romain Sonneville, Belen Cabello, Samir Jaber, Elie Azoulay, Diego Castanares-Zapatero, Jerome Devaquet, François Lellouche, Sandrine Katsahian, Laurent Brochard
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Difficult weaning from mechanical ventilation is often associated with fluid overload. B-type natriuretic peptide (BNP) has been proposed as a tool for predicting and detecting weaning failure of cardiovascular origin.Objectives: To investigate whether fluid management guided by daily BNP plasma concentrations improves weaning outcomes compared with empirical therapy dictated by clinical acumen.Methods: In a randomized controlled multicenter study, we allocated 304 patients to either a BNP-driven or physician-driven strategy of fluid management during ventilator weaning. To standardize the weaning process, patients in both groups were ventilated with an automatic computer-driven weaning system. The primary end point was time to successful extubation.Measurements and Main Results: In the BNP-driven group, furosemide and acetazolamide were given more often and in higher doses than in the control group, resulting in a more negative median (interquartile range) fluid balance during weaning (–2,320 [–4,735, 738] vs. -180 [–2,556, 2,832] ml; P < 0.0001). Time to successful extubation was significantly shorter with the BNP-driven strategy (58.6 [23.3, 139.8] vs. 42.4 [20.8, 107.5] h; P = 0.034). The BNP-driven strategy increased the number of ventilator-free days but did not change length of stay or mortality. The effect on weaning time was strongest in patients with left ventricular systolic dysfunction. The two strategies did not differ significantly regarding electrolyte imbalance, renal failure, or shock.Conclusions: Our results suggest that a BNP-driven fluid management strategy decreases the duration of weaning without increasing adverse events, especially in patients with left ventricular systolic dysfunction.Clinical trial registered with www.clinicaltrials.gov (NCT00473148).
Denis Vincent Primo D'Auria
Authors: A. O'Carroll
Journal: BMJ (2011)

After house jobs in Dublin, Denis Vincent Primo D’Auria spent three years in Italy working for the European Commission before becoming medical officer at the Atomic Energy Research Establishment (AERE) at Harwell in Oxfordshire. During a long and varied career he was medical adviser and consultant physician to South West Thames Regional Health Authority, chief medical adviser to Midland Bank (where he set up the …
Expression of the terminal protein of hepatitis B virus is associated with failure to respond to interferon therapy
Authors: Graham R. Foster, Robert D. Goldin, Andrew Hay, Michael J. McGarvey, George R. Stark, Howard C. Thomas
Journal: Hepatology (1993)

The terminal protein domain of the hepatitis B viral polymerase can inhibit the cellular response to interferon. To clarify the clinical relevance of this inhibitory effect, we examined the expression of terminal protein in liver biopsy specimens from patients with chronic hepatitis B infection. We found that expression of terminal protein is associated with a failure of hepatocytes to respond to interferon, as assessed by expression of the interferon-inducible protein beta 2-microglobulin. Patients whose liver specimens contained large numbers of cells expressing terminal protein tended not to respond to treatment. During interferon therapy the percentage of cells expressing terminal protein remained constant, but treatment significantly reduced the number of cells that expressed the hepatitis B nucleocapsid protein. Hence expression of terminal protein in a cell may prevent elimination of the virus by interferon therapy.
Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge☆☆☆
Authors: Mary Jane Thomassen, Baisakhi Raychaudhuri, Raed A. Dweik, Carol Farver, Lisa Buhrow, Anagha Malur, Mary J. Connors, Judy Drazba, Jeffrey Hammel, Serpil C. Erzurum
Journal: Journal of Allergy and Clinical Immunology (1999)
Antitumoral Activity of Lenalidomide in <i>In Vitro</i> and <i>In Vivo</i> Models of Mantle Cell Lymphoma Involves the Destabilization of Cyclin D1/p27KIP1 Complexes
Authors: Alexandra Moros, Sophie Bustany, Julie Cahu, Ifigènia Saborit-Villarroya, Antonio Martínez, Dolors Colomer, Brigitte Sola, Gaël Roué
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Clinical responses to the immmunomodulatory drug lenalidomide have been observed in patients with relapsed/refractory mantle cell lymphoma (MCL), although its mechanism of action remains partially unknown. We investigated whether the expression and subcellular localization of cyclin D1, a major cell-cycle regulator overexpressed in MCL, and the cyclin-dependent kinase inhibitor p27KIP1, could identify MCL cases sensitive to lenalidomide, and whether the compound could modulate cyclin D1/p27KIP1 complexes in MCL cells. Experimental Design: MCL primary samples and cell lines were analyzed for subcellular levels of cyclin D1/p27KIP1 complexes by Western blot, immunohistochemistry, immunoprecipitation, and flow cytometry. Activity of lenalidomide in vitro and its effect on cyclin D1/p27KIP1 complexes were evaluated by real-time PCR, immunoprecipitation, immunofluorescence, and Western blot. In vivo validation was carried out in a mouse xenograft model of human MCL. Results: We found cyclin D1 and p27KIP1 to be coordinately expressed in all the MCL samples tested. Immunoprecipitation analyses and siRNA assays suggested a direct role of cyclin D1 in the regulation of p27KIP1 levels. The nuclear accumulation of both proteins correlated with MCL cell tumorigenicity in vivo, and sensitivity to lenalidomide activity in vitro and in vivo. Lenalidomide mechanism of action relied on cyclin D1 downregulation and disruption of cyclin D1/p27KIP1 complexes, followed by cytosolic accumulation of p27KIP1, cell proliferation arrest, apoptosis, and angiogenesis inhibition. Conclusions: These results highlight a mechanism of action of lenalidomide in MCL cases with increased tumorigenicity in vivo, which is mediated by the dissociation of cyclin D1/p27KIP1 complexes, and subsequent proliferation blockade and apoptosis induction. Clin Cancer Res; 20(2); 393–403. ©2013 AACR.