tbuckley/cabot-search huggingface dataset:
Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse model
Authors: Ke-Zhi Zhang, Qiang-Bo Zhang, Quan-Bao Zhang, Hui-Chuan Sun, Jian-Yang Ao, Zong-Tao Chai, Xiao-Dong Zhu, Lu Lu, Yuan-Yuan Zhang, Yang Bu, Ling-Qun Kong, Zhao-You Tang
Journal: Journal of Hematology & Oncology (2014)

Cancer stem cells (CSCs) play a key role in the posthepatectomy recurrence of hepatocellular carcinoma (HCC). CD133+ HCC cells exhibit liver CSC–like properties, and CSC differentiation–inducing therapy may lead these cells to lose their self-renewal ability and may induce terminal differentiation, which may in turn allow their malignant potential to be controlled. Because arsenic trioxide (As2O3) increases remission rates and prolongs survival among patients with acute promyelocytic leukemia by inducing differentiation and apoptosis of leukemic cells, we hypothesized that As2O3 might also inhibit HCC recurrence and prolong survival time after hepatectomy by inducing differentiation of HCC CSCs. We evaluated the As2O3 induced differentiation of human HCC CSCs and its mechanism in vitro, and we investigated the effects of treatment with As2O3 on recurrence rates and median survival in a mouse xenograft model. We found that As2O3 induced HCC CSC differentiation by down-regulating the expression of CD133 and some stemness genes, thus inhibiting the cells' self-renewal ability and tumorigenic capacity without inhibiting their proliferation in vitro. In vivo experiments indicated that As2O3 decreased recurrence rates after radical resection and prolonged survival in a mouse model. As2O3, which shows no apparent toxicity, may induce HCC CSC differentiation by down-regulating the expression of GLI1. We found that As2O3 induced HCC CSC differentiation, inhibited recurrence, and prolonged survival after hepatectomy by targeting GLI1 expression. Our results suggest that the clinical safety and utility of As2O3 should be further evaluated.
Life-threatening effects of discontinuing inhaled nitric oxide in severe respiratory failure.
Authors: A Lavoie, J B Hall, D M Olson, M E Wylam
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We present the effects of abrupt discontinuation of inhaled nitric oxide (NO) in four patients with severe hypoxemic respiratory failure. These patients ranged from 9 mo to 65 yr of age. In each patient, after the initiation of inhaled NO, a marginal, but immediate, beneficial effect on gas exchange and, when measured, a reduction in pulmonary artery pressures was noted. However, during attempts to discontinue inhaled NO, not only did these patients develop worsening oxygenation and recrudescence of pulmonary hypertension but, unexpectedly, these parameters were worse than the baseline values, leading to life-threatening hemodynamic instability. These effects reversed immediately after reinstitution of inhaled NO. The mechanism of this severe ¿rebound¿ in pulmonary hypertension after abrupt withdrawal of NO is unclear, but its existence emphasizes the need to avoid a substantial risk to these patients. Moreover, we believe that both unintentional and intentional termination of inhaled NO therapy may lead to life-threatening deterioration in gas exchange and circulatory hemodynamics that exceeds the initial therapeutic benefit.
Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial
Authors: O Rascol, DJ Brooks, E Melamed, W Oertel, W Poewe, F Stocchi, E Tolosa
Journal: The Lancet (2005)
Bronchial challenge with flour: early response is dependent on the dose of activated allergen inhaled
Authors: D. Choudat, J.F. Fabriès, J.C. Martin, C. Villette
Journal: European Respiratory Journal (2002)

Specific bronchial challenges provide information about the relationship between inhaled dose of allergen and change in lung function, but the intermediate pathways remain largely obscure. The aim of this study was to investigate the relationships between the early asthmatic response and 1) the inhaled dose of wheat flour, 2) the concentration of wheat flour, 3) the duration of the exposure, and 4) the deactivation of inhaled allergens and mediators. Thirty-one patients with occupational asthma to wheat flour were studied. Particle aerosols were generated by a computer-controlled aerosoliser and the results were expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (FEV 1 ) (PD 20 ). The cumulative dose (from the beginning of the challenge), the last inhaled dose, and an estimated dose (taking into account exponential deactivation), were calculated. Twenty patients had high reactivity to flour (reaching a PD 20 value). Eleven patients had intermediate reactivity (no measurable PD 20 but significantly greater fall in FEV 1 compared with lactose challenge). A better correlation between change in FEV 1 and dose was obtained for the estimated dose than for the cumulative or last inhaled dose. The bronchial response to wheat flour can be measured by the individual specific hyperreactivity and is expressed by provocative dose of flour. However, deactivation of the allergen and mediators has to be taken into account. This problem can be addressed by using a mathematical model.
Digital expression profiling of novel diatom transcripts provides insight into their biological functions
Authors: Uma Maheswari, Kamel Jabbari, Jean-Louis Petit, Betina M Porcel, Andrew E Allen, Jean-Paul Cadoret, Alessandra De Martino, Marc Heijde, Raymond Kaas, Pascal J Lopez, Véronique Martin-Jézéquel, Agnès Meichenin, Thomas Mock, Micaela Schnitzler Parker, Assaf Vardi, E Virginia Armbrust, Jean Weissenbach, Michaël Katinka, Chris Bowler
Journal: Genome biology (2010)

Abstract Background Diatoms represent the predominant group of eukaryotic phytoplankton in the oceans and are responsible for around 20% of global photosynthesis. Two whole genome sequences are now available. Notwithstanding, our knowledge of diatom biology remains limited because only around half of their genes can be ascribed a function based onhomology-based methods. High throughput tools are needed, therefore, to associate functions with diatom-specific genes. Results We have performed a systematic analysis of 130,000 ESTs derived from Phaeodactylum tricornutum cells grown in 16 different conditions. These include different sources of nitrogen, different concentrations of carbon dioxide, silicate and iron, and abiotic stresses such as low temperature and low salinity. Based on unbiased statistical methods, we have catalogued transcripts with similar expression profiles and identified transcripts differentially expressed in response to specific treatments. Functional annotation of these transcripts provides insights into expression patterns of genes involved in various metabolic and regulatory pathways and into the roles of novel genes with unknown functions. Specific growth conditions could be associated with enhanced gene diversity, known gene product functions, and over-representation of novel transcripts. Comparative analysis of data from the other sequenced diatom, Thalassiosira pseudonana , helped identify several unique diatom genes that are specifically regulated under particular conditions, thus facilitating studies of gene function, genome annotation and the molecular basis of species diversity. Conclusions The digital gene expression database represents a new resource for identifying candidate diatom-specific genes involved in processes of major ecological relevance.
Genome characteristics of primary carcinomas, local recurrences, carcinomatoses, and liver metastases from colorectal cancer patients.
Authors: Chieu B Diep, Manuel R Teixeira, Lin Thorstensen, Johan N Wiig, Mette Eknæs, Jahn M Nesland, Karl-Erik Giercksky, Bertil Johansson, Ragnhild A Lothe
Journal: Molecular Cancer (2004)

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths in the Western world, and despite the fact that metastases are usually the ultimate cause of deaths, the knowledge of the genetics of advanced stages of this disease is limited. In order to identify potential genetic abnormalities underlying the development of local and distant metastases in CRC patients, we have, by comparative genomic hybridization, compared the DNA copy number profiles of 10 primary carcinomas, 14 local recurrences, 7 peritoneal carcinomatoses, and 42 liver metastases from 61 CRC patients. The median number of aberrations among the primary carcinomas, local recurrences, carcinomatoses, and liver metastases was 10, 6, 13, and 14, respectively. Several genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p, 17p, and 18, were common in all groups. In contrast, gains of 5p and 12p were more common in the carcinomatoses than in other stages of the disease. With hierarchical cluster analysis, liver metastases could be divided into two main subgroups according to clusters of chromosome changes. Each stage of CRC progression is characterized by a particular genetic profile, and both carcinomatoses and liver metastases are more genetically complex than local recurrences and primary carcinomas. This is the first genome profiling of local recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly important for the spread of the CRC cells within the peritoneal cavity.
Major limitations in knowledge of physical activity guidelines among UK medical students revealed: implications for the undergraduate medical curriculum: Table 1
Authors: Michael Dunlop, Andrew Duncan Murray
Journal: British Journal of Sports Medicine (2013)

Education of health professionals is a key element of the wider strategy to increase society's physical activity levels. To date, no study has directly assessed UK medical students' knowledge of physical activity guidelines or their ability/willingness to prescribe exercise.A questionnaire survey of final year medical students in Scottish Universities was conducted prior to a presentation on the current UK guidelines.Completed questionnaires (n=177) represented 37% of the final year cohorts. Physical inactivity was incorrectly perceived to be the least important risk factor to global mortality. 40% stated they were aware of current guidelines, but in a forced choice, 68% were able to correctly identify them for adults. In comparison, 97% correctly identified the UK's alcohol guidelines. 52% stated they felt adequately trained to give physical activity advice to the general public.The medical students in this study underestimated the risk of physical inactivity, and did not know the physical activity guidelines as well as other health promotion guidelines. A large proportion remained unconfident about giving physical activity advice. Improved education of this group is required.
Diallyl Trisulfide Suppresses Growth of PC-3 Human Prostate Cancer Xenograft <i>In vivo</i> in Association with Bax and Bak Induction
Authors: Dong Xiao, Karen L. Lew, Young-Ae Kim, Yan Zeng, Eun-Ryeong Hahm, Rajiv Dhir, Shivendra V. Singh
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The present study was undertaken to determine the effect of garlic constituent diallyl trisulfide (DATS) on growth of PC-3 human prostate cancer xenograft in vivo. Experimental Design: DATS was given orally (6 μmoL, thrice weekly) to male athymic mice s.c. implanted with PC-3 cells. Tumor sections from control and DATS-treated mice were examined for apoptotic bodies by terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay. Protein levels of apoptosis and cell cycle regulating proteins in tumor tissues of control and DATS-treated mice were determined by immunoblotting. The effect of DATS treatment on in vivo angiogenesis was determined by immunohistochemical analysis of CD31 in tumors. Results: Oral gavage of DATS significantly retarded growth of PC-3 xenografts in athymic mice without causing weight loss. For instance, 20 days after starting therapy, the average tumor volume in control mice was ∼3-fold higher compared with DATS-treated mice. Tumors from DATS-treated mice exhibited a markedly higher count of apoptotic bodies compared with control tumors. Consistent with the results in cultured PC-3 cells, the DATS-mediated suppression of PC-3 xenograft growth correlated with induction of proapoptotic proteins Bax and Bak. Although DATS treatment inhibited migration of cultured PC-3 cells in association with down-regulation of vascular endothelial growth factor receptor-2 protein, formation of new blood vessels was comparable in tumors of control and DATS-treated mice as judged by CD31 immunostaining. Conclusions: The present study indicates that DATS administration inhibits growth of PC-3 xenografts in vivo in association with induction of Bax and Bak.
Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4+ T cells.
Authors: W Y Ho, M P Cooke, C C Goodnow, M M Davis
Journal: The Journal of Experimental Medicine (1994)

Successful antibody production in vivo depends on a number of cellular events, one of the most important of these being cognate B cell-T cell interaction. To examine this phenomenon in vitro, homogeneous populations of hen egg lysozyme (HEL)-specific small resting B cells and naive CD4+ HEL-specific T cells (derived from immunoglobulin [Ig] and T cell receptor transgenic mice, respectively) were cultured together. On addition of intact HEL protein. HEL-specific B cells increase their expression of activation molecules, including a B7-related protein and CD44, and enlarge into blast cells. Within the same cultures, HEL-specific CD4+ T cells also increase expression of the activation markers CD69 and CD44, enlarge, secrete lymphokines, and proliferate. This response is radiation sensitive, supporting the conclusion that HEL-specific B cells present antigen to and activate the naive T cells. By contrast, when a synthetic peptide fragment of HEL is used to bypass B cell antigen-receptor engagement, the naive T cells enlarge and display activation antigens, but fail to produce lymphokines, proliferate, or promote B cell blastogenesis. Presentation of HEL by tolerant B cells, which are no longer able to signal effectively through their antigen receptors, results in an identical pattern of incomplete T cell activation. Addition of a stimulating anti-CD28 antibody and blocking of CD28 signals with CTLA4/Ig fusion protein both show that complete activation of naive CD4+ T cells depends on the initial induction of B7 and related costimulatory molecules after HEL binding to nontolerant HEL-specific B cells. Thus, in the absence of adequate constimulation from the B cell, naive CD4+ T cells undergo a form of "partial activation" in which they upregulate surface expression of certain T cell activation antigens, but fail to efficiently produce lymphokine and proliferate. This may explain the different conclusions that have been reached regarding the consequences of B cell antigen presentation to T cells, in that the ability of B cells to activate naive CD4+ T cells depends both on their specificity and their activation state.
Antigenic Changes of L5178Y Lymphoma After Treatment With 5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide In Vivo 2
Authors: Angelo Nicolin, Federico Spreafico, Enzo Bonmassar, Abraham Goldin
Journal: JNCI Journal of the National Cancer Institute (1976)

Immunologic alteration of the L5178Y lymphoma was obtained in vivo after treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC). A single dose of 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) "CURED" MICE CHALLENGED WITH L5178Y cells that had been treated with DIC (L5178Y/DIC) for four transplant generations; BCNU did not cure mice bearing the parent tumor. The L5178Y/DIC, treated in vivo for five transplant generations, id not grow in syngeneic mice. L5178Y/OIC cell growth and incidences of death were similar to those of parent cells when inoculated into heavily immunosuppressed mice. Adoptive transfer of lymphocytes from spleens of mice sensitized to the drug-altered tumor specifically protected immunosuppressed mice bearing the L5178Y/DIC tumor. Little protection was afforded by lymphocytes immune to the parent L5178Y tumor, whereas nonimmune lymphocytes or lymphocytes immune against unrelated tumors were completely ineffective. Anti-L5178Y/DIC lymphocytes did not cure mice challenged with the parent L5178Y tumor. Irradiated (400 R) mice previously sensitized to L5178Y/DIC cells rejected 10(2)-10(7) inocula of L5178Y/DIC cells and died when the parent L5178Y was used for challenge. It was concluded that antigeni( alterations of L5178Y cells occurred in (BALB/ctcr X DBA/2Cr)F1 mice after treatment with DIC in vivo.
cis-Decoder discovers constellations of conserved DNA sequences shared among tissue-specific enhancers
Authors: Thomas Brody, Wayne Rasband, Kevin Baler, Alexander Kuzin, Mukta Kundu, Ward F Odenwald
Journal: Genome biology (2007)

Abstract A systematic approach is described for analysis of evolutionarily conserved cis -regulatory DNA using cis- Decoder, a tool for discovery of conserved sequence elements that are shared between similarly regulated enhancers. Analysis of 2,086 conserved sequence blocks (CSBs), identified from 135 characterized enhancers, reveals most CSBs consist of shorter overlapping/adjacent elements that are either enhancer type-specific or common to enhancers with divergent regulatory behaviors. Our findings suggest that enhancers employ overlapping repertoires of highly conserved core elements.
Chronic Obstructive Pulmonary Disease and Long-Term Exposure to Traffic-related Air Pollution
Authors: Zorana J. Andersen, Martin Hvidberg, Steen S. Jensen, Matthias Ketzel, Steffen Loft, Mette Sørensen, Anne Tjønneland, Kim Overvad, Ole Raaschou-Nielsen
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood.Objectives: We assessed the effect of exposure to traffic-related air pollution over 35 years on the incidence of COPD in a prospective cohort study.Methods: We followed 57,053 participants in the Danish Diet, Cancer, and Health cohort in the Hospital Discharge Register for their first hospital admission for COPD between 1993 and 2006. We estimated the annual mean levels of nitrogen dioxide (NO2) and nitrogen oxides (NOx) at all residential addresses of the cohort participants since 1971 to an event or 2006 and used indicators of traffic near the residential address at recruitment. We assessed the association between exposure to air pollution and COPD incidence by Cox regression analyses for the full cohort, and for participants with and without comorbid conditions, including asthma, diabetes, or cardiovascular disease.Measurements and Main Results: A first hospital admission for COPD was recorded for 1,786 (3.4%) of 52,799 eligible subjects between recruitment (1993–1997) and 2006. COPD incidence was associated with the 35-year mean NO2 level (hazard ratio, 1.08; 95% confidence interval, 1.02–1.14, per interquartile range of 5.8 μg/m3), with stronger associations in subjects with diabetes (1.29; 1.05–1.50) and asthma (1.19; 1.03–1.38).Conclusions: Long-term exposure to traffic-related air pollution may contribute to the development of COPD with possibly enhanced susceptibility in people with diabetes and asthma.
The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors
Authors: Henning Stehr, Seon-Hi J Jang, José M Duarte, Christoph Wierling, Hans Lehrach, Michael Lappe, Bodo MH Lange
Journal: Molecular Cancer (2011)

Current large-scale cancer sequencing projects have identified large numbers of somatic mutations covering an increasing number of different cancer tissues and patients. However, the characterization of these mutations at the structural and functional level remains a challenge.We present results from an analysis of the structural impact of frequent missense cancer mutations using an automated method. We find that inactivation of tumor suppressors in cancer correlates frequently with destabilizing mutations preferably in the core of the protein, while enhanced activity of oncogenes is often linked to specific mutations at functional sites. Furthermore, our results show that this alteration of oncogenic activity is often associated with mutations at ATP or GTP binding sites.With our findings we can confirm and statistically validate the hypotheses for the gain-of-function and loss-of-function mechanisms of oncogenes and tumor suppressors, respectively. We show that the distinct mutational patterns can potentially be used to pre-classify newly identified cancer-associated genes with yet unknown function.
Model Development and Validation of Personal Exposure to Volatile Organic Compound Concentrations
Authors: Juana Mari Delgado-Saborit, Noel J. Aquilina, Claire Meddings, Stephen Baker, Roy M. Harrison
Journal: Environmental Health Perspectives (2009)

BackgroundDirect measurement of exposure to volatile organic compounds (VOCs) via personal monitoring is the most accurate exposure assessment method available. However, its wide-scale application to evaluating exposures at the population level is prohibitive in terms of both cost and time. Consequently, indirect measurements via a combination of microenvironment concentrations and personal activity diaries represent a potentially useful alternative.ObjectiveThe aim of this study was to optimize a model of personal exposures (PEs) based on microenvironment concentrations and time/activity diaries and to compare modeled with measured exposures in an independent data set.MaterialsVOC PEs and a range of microenvironment concentrations were collected with active samplers and sorbent tubes. Data were supplemented with information collected through questionnaires. Seven models were tested to predict PE to VOCs in 75% (n = 370) of the measured PE data set, whereas the other 25% (n = 120) was used for validation purposes.ResultsThe best model able to predict PE with independence of measurements was based upon stratified microenvironment concentrations, lifestyle factors, and individual-level activities. The proposed model accounts for 40–85% of the variance for individual VOCs and was validated for almost all VOCs, showing normalized mean bias and mean fractional bias below 25% and predicting 60% of the values within a factor of 2.ConclusionsThe models proposed identify the most important non-weather-related variables for VOC exposures; highlight the effect of personal activities, use of solvents, and exposure to environmental tobacco smoke on PE levels; and may assist in the development of specific models for other locations.
Mycobacterium kansasii pericarditis.
Authors: J A Palmer, C Watanakunakorn
Journal: Thorax (1984)

Mycobacterium kansasii was thought to exist primarily as a saprophyte until two cases of clinical infection were reported by Buhler and Pollak in 1953.'Although M kansasii is known to cause pulmonary and extrapulmonary infections, we are unable to find a previous reported case of pericarditis caused by this organism.We here describe a patient with pericarditis, pericardial effusion, and medias- tinal lymphadenitis caused by M kansasii. Case reportA 75 year old black man was admitted to hospital with a one year history of intermittent cough, mucoid sputum, fever, chills, and night sweats, together with gradual weight