tbuckley/cabot-search huggingface dataset:
PTH-088 Non Invasive Monitoring Of Fatty Livers In Morbidly Obese Patients: Preliminary Evaluation With Acoustic Radiation Force Impulse Imaging
Authors: S Chakravartty, O Jaffer, Y Zen, J Dent, J Clarke, P Sidhu, A Patel
Journal: Gut (2014)

<h3>Introduction</h3> Liver biopsy remains the gold standard for diagnosing non-alcoholic steatohepatitis (NASH). But with a variability of 10–20% and a mortality rate of 0.01%, non invasive techniques of monitoring change in liver morphology have been sought after. Acoustic radiation force impulse imaging (ARFI) is a promising innovation that combines ultrasound imaging and elastography to measure liver stiffness which correlates well with liver fibrosis. Morbidly obese patients are at a risk of developing NASH or Non Alcoholic Fatty Liver Disease (NAFLD) and weight loss helps improve liver steatosis. Very low calorie diets (VLCD) help in weight reduction and are known to shrink the liver. Our aim was to assess the role of ARFI in assessing and monitoring the change in liver architecture in a cohort of morbidly obese patients in response to VLCD. <h3>Methods</h3> A cohort of non-diabetic morbidly obese patients at risk for NASH was selected for this study (clinical trial no: NCT01950052). Liver volume was estimated with the help of a standardised ultrasound protocol while liver fibrosis was analysed with ARFI. After randomisation, a very low calorie diet (800 kcal) was given to one group while the rest were controls. Four weeks later, ARFI was repeated and all patients underwent a laparoscopic roux-en-y gastric bypass. A liver biopsy was taken during surgery from the same liver segment as the ARFI measurements. The liver histology was evaluated according to the NASH Clinical Research Network Scoring System by two blinded pathologists. Steatosis, fibrosis and NAFLD activity scores were correlated with ARFI scores. <h3>Results</h3> Liver volume shrank by 21.5% in the diet arm (n = 10) compared to 2% (p &lt; 0.05) in the control arm (n = 14) in 4 weeks. The ARFI scores were similar in the diet and control group [median 2.92 (1.1–3.8) m/s vs. 3.22 (1.54–3.65) m/s, p = 0.7], p = 0.7] at recruitment and at the time of the biopsy 4 weeks later [2.16 (1.19–3.68) m/s vs. 2.83 (1.5–3.48) m/s, p = 0.3]. ARFI demonstrated a drop in values in the diet group (p = 0.1) but this was not significant. Similarly, liver biopsy at surgery confirmed a trend of lower levels of steatosis in the diet group (27 vs. 42%, p = 0.12). The ARFI scores did not correlate with the steatosis grade (p = 0.8), or NAFLD score (p = 0.48). <h3>Conclusion</h3> Low calorie diets shrink liver volumes but ARFI could not detect any change in liver stiffness. ARFI does not appear to correlate with liver steatosis and may not be ideally suited for short term monitoring of successful treatment of NASH. However its role in long term monitoring needs further evaluation. <h3>Disclosure of Interest</h3> None Declared.
Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy
Authors: Karen K. Ballen, Pamela S. Becker, Robert V. B. Emmons, Thomas J. Fitzgerald, Chung C. Hsieh, Qin Liu, Christine Heyes, Yeteive Clark, William Levy, Jean Francois Lambert, Frank Chiafari, Irma Szymanski, Sarah Rososhansky, Mark A. Popovsky, F. Marc Stewart, Peter J. Quesenberry
Journal: Blood (2002)
Evolutionary internalized regularities
Authors: Robert Schwartz
Journal: Behavioral and Brain Sciences (2001)

Roger Shepard's proposals and supporting experiments concerning evolutionary internalized regularities have been very influential in the study of vision and in other areas of psychology and cognitive science. This paper examines issues concerning the need, nature, explanatory role, and justification for postulating such internalized constraints. In particular, I seek further clarification from Shepard on how best to understand his claim that principles of kinematic geometry underlie phenomena of motion perception. My primary focus is on the ecological validity of Shepard's kinematic constraint in the context of ordinary motion perception. First, I explore the analogy Shepard draws between internalized circadian rhythms and the supposed internalization of kinematic geometry. Next, questions are raised about how to interpret and justify applying results from his own and others' experimental studies of apparent motion to more everyday cases of motion perception in richer environments. Finally, some difficulties with Shepard's account of the evolutionary development of his kinematic constraint are considered.
International Expert Consensus Statement
Authors: Markus P. Schlaich, Roland E. Schmieder, George Bakris, Peter J. Blankestijn, Michael Böhm, Vito M. Campese, Darrel P. Francis, Guido Grassi, Dagmara Hering, Richard Katholi, Sverre Kjeldsen, Henry Krum, Felix Mahfoud, Giuseppe Mancia, Franz H. Messerli, Krzysztof Narkiewicz, Gianfranco Parati, Krishna J. Rocha-Singh, Luis M. Ruilope, Lars C. Rump, Domenic A. Sica, Paul A. Sobotka, Costas Tsioufis, Oliver Vonend, Michael A. Weber, Bryan Williams, Thomas Zeller, Murray D. Esler
Journal: Journal of the American College of Cardiology (2013)
The Phenotypic Plasticity of Myeloma Plasma Cells as Expressed by Dedifferentiation into an Immature, Resilient, and Apoptosis-Resistant Phenotype
Authors: Shmuel Yaccoby
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We previously showed the ability of osteoclasts to support myeloma plasma cell survival and proliferation in vivo and ex vivo. The aim of the current study was to investigate osteoclast-induced phenotypic changes associated with long-term survival of myeloma cells in coculture. Experimental Design: CD138-selected myeloma plasma cells from 16 patients were cocultured with human osteoclasts for up to 20 weeks. Results: Precultured cells were typically CD45low/intermediate CD38high CD138high, CD19−CD34−. After &amp;gt;6 weeks, the phenotype of cocultured myeloma cells consistently shifted to cells expressing CD45intermediate/high CD19low CD34low. Expression of CD38 and CD138 were reduced to subpopulations with CD38intermediate and CD138low levels. Morphologically, cocultured plasma cells became plasmablastic. Blocking interleukin-6 activity did not affect the immature phenotype of myeloma cells. The effect of dexamethasone on myeloma cells cultured alone or in cocultures at baseline and after 6 weeks of coculture was determined. When baseline myeloma cells were cultured alone, dexamethasone significantly increased the percentage of apoptotic cells over the spontaneous rate. Conversely, myeloma cells recovered from cocultures had high survival rates and were resistant to dexamethasone-induced apoptosis. Long-term coculture of normal CD34-expressing hematopoietic stem cells (HSC) resulted in loss of CD34 expression, suggesting a common mechanism for osteoclast-induced myeloma and HSC plasticity. Conclusions: This study indicates that myeloma cells have plasticity expressed by their ability to reprogram, dedifferentiate, and acquire autonomous survival properties.
A Role for Endothelin-2 and Its Receptors in Breast Tumor Cell Invasion
Authors: Matthew J. Grimshaw, Thorsten Hagemann, Ayse Ayhan, Cheryl E. Gillett, Claudia Binder, Frances R. Balkwill
Journal: Cancer Research (2004)

Abstract We have studied the role of endothelins (ET-1, ET-2 and ET-3) and ET receptors (ET-RA and ET-RB) in the invasive capacity of breast tumor cells, which express ET-1 and ET-2 as well as ET-RA and ET-RB. Of five human breast tumor cell lines tested, all expressed mRNAs for ET-1, ET-2, and ET-RB. ET-RA mRNA was expressed by four of five tumor cell lines. Breast tumor cells migrated toward ET-1 and ET-2 but not toward ET-3. Chemotaxis involved signaling via both receptors, and a pertussis toxin-sensitive p42/p44 mitogen-activated protein kinase (MAPK)-mediated pathway that could be inhibited by MAPK kinase (MEK)1/2 antagonists. Chemotaxis toward ETs did not involve p38 or stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) and was not inhibited by hypoxia. Incubation of tumor cells with ET-2 also increased chemotaxis toward the chemokines CXCL12 and CCL21. As well as inducing chemotaxis of tumor cells, ET-1 and ET-2 increased tumor cell invasion through Matrigel. Furthermore, stimulation of macrophage/tumor cell cocultures with ETs led to increased matrix metalloproteinase (MMP)-2 and -9 production by macrophages and a marked increase in invasion of tumor cells. Antagonism of either ET-RA or ET-RB decreased the invasion seen in ET-stimulated cocultures, as did a broad-spectrum MMP inhibitor. Immunohistochemical staining of human breast tumor sections showed increased ET and ET receptor protein expression by tumor cells in invasive ductal carcinoma compared with normal breast tissue or ductal carcinoma in situ. Furthermore, tumor cell ET and receptor expression was stronger at the invasive margin of invasive ductal carcinomas, in the lymphovascular space, and in lymph node metastases. ET expression often colocalized with ET-RB expression in all neoplastic tissue indicating a possible autocrine action of ETs. We suggest that expression of ETs and their receptors by human breast tumors, particularly in conjunction with a high macrophage infiltrate, may have a role in the progression of breast cancer and the invasion of tumor cells.
Fenretinide Cytotoxicity for Ewing’s Sarcoma and Primitive Neuroectodermal Tumor Cell Lines Is Decreased by Hypoxia and Synergistically Enhanced by Ceramide Modulators
Authors: Sandeep Batra, C. Patrick Reynolds, Barry J. Maurer
Journal: Cancer Research (2004)

Abstract Patients with disseminated Ewing’s family of tumors (ESFT) often experience drug-resistant relapse. We hypothesize that targeting minimal residual disease with the cytotoxic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR; fenretinide) may decrease relapse. We determined the following: (a) 4-HPR cytotoxicity against 12 ESFT cell lines in vitro; (b) whether 4-HPR increased ceramide species (saturated and desaturated ceramides); (c) whether physiological hypoxia (2% O2) affected cytotoxicity, mitochondrial membrane potential (ΔΨm) change, or ceramide species or reactive oxygen species levels; (d) whether cytotoxicity was enhanced by l-threo-dihydrosphingosine (safingol); (e) whether physiological hypoxia increased acid ceramidase (AC) expression; and (f) the effect of the AC inhibitor N-oleoyl-ethanolamine (NOE) on cytotoxicity and ceramide species. Ceramide species were quantified by thin-layer chromatography and scintillography. Cytotoxicity was measured by a fluorescence-based assay using digital imaging microscopy (DIMSCAN). Gene expression profiling was performed by oligonucleotide array analysis. We observed, in 12 cell lines tested in normoxia (20% O2), that the mean 4-HPR LC99 (the drug concentration lethal to 99% of cells) = 6.1 ± 5.4 μm (range, 1.7–21.8 μm); safingol (1–3 μm) synergistically increased 4-HPR cytotoxicity and reduced the mean 4-HPR LC99 to 3.2 ± 1.7 μm (range, 2.0–8.0 μm; combination index &amp;lt; 1). 4-HPR increased ceramide species in the three cell lines tested (up to 9-fold; P &amp;lt; 0.05). Hypoxia (2% O2) reduced ceramide species increase, ΔΨm loss, reactive oxygen species increase (P &amp;lt; 0.05), and 4-HPR cytotoxicity (P = 0.05; 4-HPR LC99, 19.7 ± 23.9 μm; range, 2.3–91.4). However, hypoxia affected 4-HPR + safingol cytotoxicity to a lesser extent (P = 0.04; 4-HPR LC99, 4.9 ± 2.3 μm; range, 2.0–8.2). Hypoxia increased AC RNA expression; the AC inhibitor NOE enhanced 4-HPR-induced ceramide species increase and cytotoxicity. The antioxidant N-acetyl-l-cysteine somewhat reduced 4-HPR cytotoxicity but did not affect ceramide species increase. We conclude the following: (a) 4-HPR was active against ESFT cell lines in vitro at concentrations achievable clinically, but activity was decreased in hypoxia; and (b) combining 4-HPR with ceramide modulators synergized 4-HPR cytotoxicity in normoxia and hypoxia.
British pilot study of exercise therapy. I. Middle-aged men.
Authors: M. E. Carruthers, R. H. Edwards, N. B. Pride, P. Nixon, C. De Moncheaux
Journal: British Journal of Sports Medicine (1976)

The physiological and biochemical effects of a carefully graduated course of vigorous gymnasium training with two or three weekly exercise sessions lasting only 15 minutes have been studied in middle-aged London business men. Activity diaries and psychological questionnaires indicated that these men had a positive attitude to exercise which was probably greater than average. The gymnasium exercises caused a large oxygen debt and considerable rises in plasma catecholamines and lactate levels. A close correlation was found between the pulse rate during exercise and the Borg scale of perceived exertion, so that both could be used to ensure that short periods of exercise were sufficiently vigorous to produce a training effect, and protect against over-exertion. The acceptability of this particular exercise regime was shown by the low fall-out and injury rate. It is suggested that this exercise training programme possesses many features which are advantageous if increased physical activity is to be more widely used as a method of reducing some of the risk factors in coronary heart disease.
Increased frequency of cystic fibrosis deltaF508 mutation in bronchiectasis associated with rheumatoid arthritis
Authors: X Puechal, I Fajac, T Bienvenu, N Desmazes-Dufeu, D Hubert, JC Kaplan, CJ Menkes, DJ Dusser
Journal: European Respiratory Journal (1999)

This study investigated the clinical characteristics and the possible involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in patients with symptomatic diffuse bronchiectasis (DB) associated with rheumatoid arthritis (RA). Twenty-six patients with both RA and DB (group RA+DB) and control groups of 29 consecutive patients with RA but no bronchiectasis (group RA) and 29 patients with symptomatic DB of unknown origin (group DB) were prospectively studied. Among the patients of the RA+DB group, four (15.4%) were heterozygous for the CFTR gene deltaF508 mutation, whereas no deltaF508 mutation was found in patients of the RA and the DB groups (both, p<0.05). This frequency of deltaF508 mutation was also higher than the expected frequency (2.8%) in the general European population (p<0.04). Sweat chloride values and nasal potential differences were normal in three out of four patients carrying the deltaF508 mutation. In the RA+DB group, those with deltaF508 mutation had more frequent chronic sinusitis (p<0.05), a trend toward a more severe pulmonary involvement, and a lower value of nasal potential differences (p<0.01) whereas their rheumatic features had no particularity. In the RA+DB group, patients with adult-onset bronchiectasis (including two with deltaF508 mutation) had a greater reduction in total lung capacity (p<0.05) and lower nasal potential differences (p<0.005) than those with childhood-onset bronchiectasis. This study suggests a possible deleterious effect of the cystic fibrosis transmembrane conductance regulator mutated protein in the airways which may predispose to the development and severity of bronchiectasis in patients suffering from rheumatoid arthritis.
Translating Nutrition Science into Policy as Witness and Actor
Authors: Irwin H. Rosenberg
Journal: Annual Review of Nutrition (2008)

The sustained effort to witness and participate in the targeted translation of nutritional science and policy forms the structure of this narrative. The memoir starts with an early career-directing experience with nutrition and cholera and proceeds with a long thread of interest in folic acid malabsorption as one of the determinants of nutritional anemia in Asia and the tropics. The thread continues with the relationship of folate and associated vitamins to brain function and aging as a prototype of the study of the interface of aging biology and nutritional biology. My current interest in world hunger and famine and their impact on human security may circle back to studies of the great Bengal famine and the first Bangladesh survey of malnutrition.
Serum levels of interferon do not correlate with disease activity in patients with dermatomyositis/polymyositis
Authors: P. Krol, O. Krystufkova, M. Polanska, H. Mann, M. Klein, O. Beran, J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2010)

Idiopathic inflammatory myopathies include three major diseases: dermatomyositis (DM), polymyositis (PM) and inclusion body myositis.1,–,3 The ethiopathogenesis of these entities is still not well understood. Recent studies show an important role of type I interferon (IFN) in the proinflammatory process leading to disease manifestations in muscle tissue.4,–,6

In order to investigate the relationship of soluble IFNα serum levels with clinical and laboratory characteristics we analysed serum samples of 43 patients with DM/PM (24/19 patients with DM and PM, respectively; 32 women/11 men). Patients were selected from a cohort of 81 PM/DM cases with the preference for those who were anti-Jo-1 positive, and had muscle MRI performed. In total, 44% of patients (n=19) were not treated prior to the collection of blood samples (group 1). Patients treated with ≤20 mg of prednisone per day at the time of blood draw were assigned to group 2 …
Elevated Incidence of Type 2 Diabetes in San Antonio, Texas, Compared With That of Mexico City, Mexico
Authors: James P. Burke, Ken Williams, Steven M. Haffner, Clicerio Gonzalez Villalpando, Michael P. Stern
Journal: Diabetes Care (2001)

OBJECTIVE—To compare the incidence of type 2 diabetes between low-income Mexican-Americans residing in San Antonio, Texas, and low-income residents in Mexico City, Mexico. RESEARCH DESIGN AND METHODS—Using data from the San Antonio Heart Study and the Mexico City Diabetes Study, we compared the incidence of type 2 diabetes in 35- to 64-year-old low-income Mexican-American residents of San Antonio with similarly aged low-income residents of Mexico City. Because of the different follow-up times in the two studies, Poisson regression was used to compare the rates of diabetes. Potential risk factors for diabetes were also analyzed to determine whether they explained or contributed to a difference in incidence. RESULTS—The age- and sex-adjusted incidence of type 2 diabetes was significantly higher in San Antonio (RR 2.01) compared with Mexico City. This difference was seen primarily in the oldest age group (55–64 years of age) and remained statistically significant after adjusting for a number of diabetes risk factors, including demographic, anthropometric, and metabolic variables. Follow-up rates were similar in both cities. CONCLUSIONS—We conclude that there was a higher incidence of type 2 diabetes in San Antonio than in Mexico City, and that difference occurred primarily in individuals in the oldest age group. The potential mediating factors we examined did not account for this difference. Other factors, such as exercise and diet, which were not available for analysis in this study, in addition to a cohort effect, may have contributed to the difference in incidence of type 2 diabetes in the two cities. In addition, there was no evidence of a higher case fatality among diabetic individuals from Mexico City compared with San Antonio.
Xg Expression in Ewing's Sarcoma Is of Prognostic Value and Contributes to Tumor Invasiveness
Authors: Ophélie Meynet, Katia Scotlandi, Emmanuelle Pradelli, Maria C. Manara, Mario P. Colombo, Heidy Schmid-Antomarchi, Piero Picci, Alain Bernard, Ghislaine Bernard
Journal: Cancer Research (2010)

Abstract Ewing's sarcoma (EWS) is an aggressive tumor of children and young adults that requires intensive treatment. The search for new prognostic factors is very important to choose the most appropriate therapy and to better understand the biology of the disease for the development of new therapeutic tools. We found that Xg, a thus far poorly described molecule and member of the CD99 family, is expressed in EWS cell lines and EWS primary tumors. Immunohistochemical analysis confirmed the expression of Xg in 24% of patients. We found that Xg expression in EWS defines a subgroup of patients with worse prognosis compared with those with Xg-negative localized tumors, indicating a clinical relevance of Xg expression in EWS. Forced expression of Xg in an EWS cell line upregulated cell migration and invasion in vitro. Furthermore, knockdown of Xg expression with specific short hairpin RNA significantly reduced migration and invasion of EWS cells. Consistent with these data, in vivo xenotransplant studies in nude mice revealed that Xg expression increased the incidence and the number of metastases of EWS cells. Thus, Xg expression is associated with lower overall survival in EWS patients with localized tumors and is implicated in metastasis. Cancer Res; 70(9); 3730–8. ©2010 AACR.
Prognostic Utility of Heart-Type Fatty Acid Binding Protein in Patients With Acute Coronary Syndromes
Authors: Michelle O’Donoghue, James A. de Lemos, David A. Morrow, Sabina A. Murphy, Jacqueline L. Buros, Christopher P. Cannon, Marc S. Sabatine
Journal: Circulation (2006)

Background— Heart-type fatty acid binding protein (H-FABP) is a cytosolic protein that is released rapidly from the cardiomyocyte in response to myocardial injury. Although it has been investigated as an early marker of acute myocardial infarction, its prognostic utility in acute coronary syndromes has not been established. Methods and Results— We measured H-FABP in 2287 patients with acute coronary syndromes from the OPUS-TIMI 16 trial. H-FABP was elevated (&gt;8 ng/mL) in 332 patients (14.5%). Patients with an elevated H-FABP were more likely to suffer death (hazard ratio [HR], 4.1; 95% CI, 2.6 to 6.5), recurrent myocardial infarction (HR, 1.6; 95% CI, 1.0 to 2.5), congestive heart failure (HR, 4.5; 95% CI, 2.6 to 7.8), or the composite of these end points (HR, 2.6; 95% CI, 1.9 to 3.5) through the 10-month follow-up period. H-FABP predicted the risk of the composite end point both in patients who were troponin I negative (HR, 2.1; 95% CI, 1.3 to 3.4) and in those who were troponin I positive (HR, 3.3; 95% CI, 2.0 to 5.3). In a Cox proportional-hazards model that adjusted for baseline variables, including demographics, clinical characteristics, creatinine clearance, ST deviation, index diagnosis, and troponin I, elevated H-FABP remained a significant predictor of the composite end point (HR, 1.9; 95% CI, 1.3 to 2.7), as well as the individual end points of death (HR, 2.7; 95% CI, 1.5 to 4.9) and CHF (HR, 2.4; 95% CI, 1.2 to 5.0). In a multimarker approach, H-FABP, troponin I, and B-type natriuretic peptide provided complementary information. Conclusions— Elevation of H-FABP is associated with an increased risk of death and major cardiac events in patients presenting across the spectrum of acute coronary syndromes and is independent of other established clinical risk predictors and biomarkers.