tbuckley/cabot-search huggingface dataset:
BMI-1 Promotes Ewing Sarcoma Tumorigenicity Independent of<i>CDKN2A</i>Repression
Authors: Dorothea Douglas, Jessie Hao-Ru Hsu, Long Hung, Aaron Cooper, Diana Abdueva, John van Doorninck, Grace Peng, Hiro Shimada, Timothy J. Triche, Elizabeth R. Lawlor
Journal: Cancer Research (2008)

Abstract Deregulation of the polycomb group gene BMI-1 is implicated in the pathogenesis of many human cancers. In this study, we have investigated if the Ewing sarcoma family of tumors (ESFT) expresses BMI-1 and whether it functions as an oncogene in this highly aggressive group of bone and soft tissue tumors. Our data show that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI-1 actively promotes anchorage-independent growth in vitro and tumorigenicity in vivo. Moreover, we find that BMI-1 promotes the tumorigenicity of both p16 wild-type and p16-null cell lines, demonstrating that the mechanism of BMI-1 oncogenic function in ESFT is, at least in part, independent of CDKN2A repression. Expression profiling studies of ESFT cells following BMI-1 knockdown reveal that BMI-1 regulates the expression of hundreds of downstream target genes including, in particular, genes involved in both differentiation and development as well as cell-cell and cell-matrix adhesion. Gain and loss of function assays confirm that BMI-1 represses the expression of the adhesion-associated basement membrane protein nidogen 1. In addition, although BMI-1 promotes ESFT adhesion, nidogen 1 inhibits cellular adhesion in vitro. Together, these data support a pivotal role for BMI-1 ESFT pathogenesis and suggest that its oncogenic function in these tumors is in part mediated through modulation of adhesion pathways. [Cancer Res 2008;68(16):6507–15]
Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity
Authors: Felix C. Weber, Philipp R. Esser, Tobias Müller, Jayanthi Ganesan, Patrizia Pellegatti, Markus M. Simon, Robert Zeiser, Marco Idzko, Thilo Jakob, Stefan F. Martin
Journal: The Journal of Experimental Medicine (2010)

Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X(7) are resistant to contact hypersensitivity (CHS). P2X(7)-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X(7) antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X(7)-deficient mice. Thus, P2X(7) is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X(7) triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X(7) signaling may be a promising strategy for the prevention of allergic contact dermatitis.
Using serum osteopontin to help identify pleural mesothelioma
Authors: C K Hui
Journal: Thorax (2006)

▴ Pass HI, Lott D, Lonardo F et al . Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med2005;353:1564–73

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



Serum osteopontin levels were compared in 76 patients with surgically staged pleural mesothelioma, 69 with non-malignant asbestos disease, and 45 non-exposed controls. Tumour osteopontin was also assessed in the patients with mesothelioma.

Comparing age matched subjects with and without exposure to asbestos …

 [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DPass%26rft.auinit1%253DH.%2BI.%26rft.volume%253D353%26rft.issue%253D15%26rft.spage%253D1564%26rft.epage%253D1573%26rft.atitle%253DAsbestos%2Bexposure%252C%2Bpleural%2Bmesothelioma%252C%2Band%2Bserum%2Bosteopontin%2Blevels.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa051185%26rft_id%253Dinfo%253Apmid%252F16221779%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx
 [2]: /lookup/external-ref?access_num=10.1056/NEJMoa051185&link_type=DOI
 [3]: /lookup/external-ref?access_num=16221779&link_type=MED&atom=%2Fthoraxjnl%2F61%2F1%2F22.atom
 [4]: /lookup/external-ref?access_num=000232486000010&link_type=ISI
Valsartan regulates the interaction of angiotensin II type 1 receptor and endothelial nitric oxide synthase via Src/PI3K/Akt signalling
Authors: Kuo-Hui Su, Jin-Yi Tsai, Yu Ru Kou, An-Na Chiang, Sheng-Huang Hsiao, Yuh-Lin Wu, Hsin-Han Hou, Ching-Chian Pan, Song-Kun Shyue, Tzong-Shyuan Lee
Journal: Cardiovascular Research (2009)

Valsartan, a selective angiotensin II type 1 receptor (AT1R) blocker, has beneficial effects in the cardiovascular system in part by its increase of nitric oxide (NO) bioavailability, yet the mechanisms are unclear. We investigated the molecular mechanisms underlying this effect in endothelial cells (ECs). NO production was examined by Griess reagent assay, DAF-2 DA fluorescence staining and cGMP ELISA kits. Protein interaction was determined by western blotting and immunoprecipitation. Treating bovine or human aortic ECs with valsartan increased NO production, as evidenced by elevated level of stable NO metabolites and intracellular cGMP. Valsartan increased the phosphorylation but not the protein level of endothelial NO synthase (eNOS). Inhibition of phosphoinositide-3 kinase (PI3K)/Akt and Src pathways by specific inhibitors suppressed valsartan-induced NO release. In addition, valsartan increased the tyrosine residue phosphorylation of AT1R, which was attenuated by inhibition of Src but not PI3K activities. Valsartan also suppressed the interaction of eNOS and AT1R, which was blocked by Src or PI3K inhibition. Valsartan-induced NO production in ECs is mediated through Src/PI3K/Akt-dependent phosphorylation of eNOS. Valsartan-induced AT1R phosphorylation depends on Src but not PI3K, whereas valsartan-induced suppression of AT1R–eNOS interaction depends on Src/PI3K/Akt signalling. These results indicate a novel vasoprotective mechanism of valsartan in upregulating NO production in ECs.
[<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography Predicts Survival After Chemoimmunotherapy for Primary Mediastinal Large B-Cell Lymphoma: Results of the International Extranodal Lymphoma Study Group IELSG-26 Study
Authors: Maurizio Martelli, Luca Ceriani, Emanuele Zucca, Pier Luigi Zinzani, Andrés J.M. Ferreri, Umberto Vitolo, Caterina Stelitano, Ercole Brusamolino, Maria Giuseppina Cabras, Luigi Rigacci, Monica Balzarotti, Flavia Salvi, Silvia Montoto, Armando Lopez-Guillermo, Erica Finolezzi, Stefano A. Pileri, Andrew Davies, Franco Cavalli, Luca Giovanella, Peter W.M. Johnson
Journal: Journal of Clinical Oncology (2014)

To assess the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) after rituximab and anthracycline-containing chemoimmunotherapy in patients with primary mediastinal large B-cell lymphoma (PMLBCL).Among 125 patients prospectively enrolled, 115 were eligible for central review of PET/CT scans at the completion of standard chemoimmunotherapy, by using a five-point scale. Consolidation radiotherapy (RT) was permitted and given to 102 patients.Fifty-four patients (47%) achieved a complete metabolic response (CMR), defined as a completely negative scan or with residual [18F]FDG activity below the mediastinal blood pool (MBP) uptake. In the remaining 61 patients (53%), the residual uptake was higher than MBP uptake but below the liver uptake in 27 (23%), slightly higher than the liver uptake in 24 (21%), and markedly higher in 10 (9%). CMR after chemoimmunotherapy predicted higher 5-year progression-free survival (PFS; 98% v 82%; P=.0044) and overall survival (OS; 100% v 91%; P=.0298). Patients with residual uptake higher than MBP uptake but below liver uptake had equally good outcomes without any recurrence. Using the liver uptake as cutoff for PET positivity (boundary of score, 3 to 4) discriminated most effectively between high or low risk of failure, with 5-year PFS of 99% versus 68% (P<.001) and 5-year OS of 100% versus 83% (P<.001).More than 90% of patients are projected to be alive and progression-free at 5 years, despite a low CMR rate (47%) after chemoimmunotherapy. This study provides a basis for using PET/CT to define the role of RT in PMLBCL.
Small bowel transit of a bran meal residue in humans: sieving of solids from liquids and response to feeding
Authors: J M Hebden, P E Blackshaw, A C Perkins, M D’Amato, R C Spiller
Journal: Gut (1998)

Background —Ileal motor patterns are adapted to the propulsion of viscous meal residue, such as bran, which accumulates in the distal ileum postprandially. Aims —To examine the effects of a second liquid/solid meal on ileal emptying. Subjects and methods —Eleven healthy fasting subjects consumed a 1.47 MJ pancake containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A). Gastric emptying and transit through the left upper quadrant (proximal) and right lower quadrant (distal) small bowel regions and colon were assessed scintigraphically. Transit was compared with and without a second Indium-111 liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first meal. Results —Gastric emptying of meal A was slower than meal B (the time for 50% of the activity to leave the stomach (T 50 ) being 113 (11) minutes versus 48 (3) minutes respectively, p&lt;0.01, n=11). Both meals passed rapidly through the proximal small bowel (T 50 meal A = 57 (14) minutes versus T 50 meal B = 42 (11) minutes). Transit of meal A through the distal small bowel was much slower (T 50 more than 390 minutes versus 176 (29) minutes for meal B, p&lt;0.01), resulting in meal B overtaking meal A and entering the colon earlier. Ingestion of the second meal (B) resulted in significantly less meal A marker entering the colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p&lt;0.05, n=8). Conclusions —The distal small bowel selectively retains bran, allowing liquid phase markers through to the colon. Consuming a second liquid/solid meal does not stimulate ileal transit of bran which seems to be propelled quicker by fasting motor patterns.
The quality of life in acne: a comparison with general medical conditions using generic questionnaires
Authors: None MALLON, None NEWTON, None KLASSEN, None STEWART-BROWN, None RYAN, None FINLAY
Journal: British Journal of Dermatology (1999)

Skin diseases such as acne are sometimes thought of as unimportant, even trivial, when compared with diseases of other organ systems. To address this point directly, validated generic questionnaires were used to assess morbidity in acne patients and compare it with morbidity in patients with other chronic diseases. For 111 acne patients referred to a dermatologist, quality of life was measured using the Dermatology Life Quality Index, Rosenberg's measure of self‐esteem, a version of the General Health Questionnaire (GHQ‐28) and the Short Form 36 (SF‐36). Clinical severity was measured using the Leeds Acne Grade. Population quality of life data for the SF‐36 instrument were available from a random sample of adult local residents (n = 9334) some of whom reported a variety of long‐standing disabling diseases. All quality of life instruments showed substantial deficits for acne patients that correlated with each other but not with clinically assessed acne severity. The acne patients (a relatively severely affected group) reported levels of social, psychological and emotional problems that were as great as those reported by patients with chronic disabling asthma, epilepsy, diabetes, back pain or arthritis. Acne is not a trivial disease in comparison with other chronic conditions. This should be recognized in the allocation of health care resources.
Regional Brain Activity in Women Grieving a Romantic Relationship Breakup
Authors: Arif Najib, Jeffrey P. Lorberbaum, Samet Kose, Daryl E. Bohning, Mark S. George
Journal: American Journal of Psychiatry (2004)

Separation from loved ones commonly leads to grief reactions. In some individuals, grief can evolve into a major depressive episode. The brain regions involved in grief have not been specifically studied. The authors studied brain activity in women actively grieving a recent romantic relationship breakup. It was hypothesized that while remembering their ex-partner, subjects would have altered brain activity in regions identified in sadness imaging studies: the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex.Nine right-handed women whose romantic relationship ended within the preceding 4 months were studied. Subjects were scanned using blood-oxygen-level-dependent functional magnetic resonance imaging while they alternated between recalling a sad, ruminative thought about their loved one (grief state) and a neutral thought about a different person they knew an equally long time.Acute grief (grief minus neutral state) was associated with increased group activity in posterior brain regions, including the cerebellum, posterior brainstem, and posterior temporoparietal and occipital brain regions. Decreased activity was more prominent anteriorly and on the left and included the anterior brainstem, thalamus, striatum, temporal cortex, insula, and dorsal and ventral anterior cingulate/prefrontal cortex. When a more lenient statistical threshold for regions of interest was used, additional increases were found in the lateral temporal cortex, supragenual anterior cingulate/medial prefrontal cortex, and right inferomedial dorsolateral prefrontal cortex, all of which were adjacent to spatially more prominent decreases. In nearly all brain regions showing brain activity decreases with acute grief, activity decreases were greater in women reporting higher grief levels over the past 2 weeks.During acute grief, subjects showed brain activity changes in the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex, consistent with the hypothesis. Subjects with greater baseline grief showed greater decreases in all these regions except for the cerebellum. Further imaging studies are needed to understand the relationship between normal sadness, grief, and depression.
A blueprint for bone health across the lifespan: engaging novel team members to influence fracture rates
Authors: S K Boyd, R E Rhodes, J Wharf Higgins, H A McKay, K M Khan
Journal: British Journal of Sports Medicine (2011)

Physical activity is a key, and increasingly recognised lifestyle determinant of bone health. For the mildly sceptical reader, we remind you that 26% of adult bone mass is laid down in two growing years around puberty,1 resistance training mitigates a proportion of postmenopausal bone loss and Cochrane systematic reviews conclude that strength and balance training reduce falls by 35% (and thus, fall-related fractures) in older people. A 2008 BMJ cover article emphasised that preventing falls was key in the battle against fractures. The term, ‘fall-related’ is a more accurate primary label than ‘osteoporotic’ for appendicular fractures among older people. And 80% of fractures occur in those who do not have osteoporosis.2

Nihilism has no place when physical activity is a proven therapeutic agent. But there is also no point in adding to the long list of cross-sectional or athlete studies showing that exercise is associated with greater bone mass as measured by dual-energy x-ray absorptiometry (DXA). There are many great options and we admire the body of brilliant work in bone science and activity going on all over the globe. Here, we respectfully outline a few possible next steps in the spirit of sharing, capacity building and teamwork. Think Wikinomics rather than Moses' tablets.

There has been a rightful emphasis on randomised controlled trials (RCTs) (and systematic reviews) with the wisdom of evidence-based practice. It behooves us to recall that well-executed cohort studies complement RCTs. The Study of Osteoporotic Fractures and EPIDOS are just two of many wonderful bone cohort studies that point to mechanisms, address the inter-related determinants that are a factor of real life and provide a great opportunity for …
STUDIES OF CALCIUM AND PHOSPHORUS METABOLISM
Authors: Walter Bauer, Joseph C. Aub, Fuller Albright
Journal: The Journal of Experimental Medicine (1929)

1. Bone trabeculae are easily depleted by the prolonged administration of parathormone, long continued negative calcium balance and growth. 2. A long continued high calcium diet results in a rapid accumulation of the trabeculae. 3. Alizarin red, as has previously been shown in the literature, is deposited in newly formed bone. Its use has made clear that easily mobilizable calcium is not deposited in the shafts of adult animals, but in the trabeculae of bone. 4. The bone trabeculae therefore serve as the storehouse of readily available calcium. 5. The shafts have a slow progressive exchange of inorganic salts and are not influenced except in the case of unusual body demands. 6. It is suggested that the absence of trabeculae in premature infants and their depletion at the end of 4 months in a normal baby might well be an etiological factor in rickets. 7. In our observations, parathormone administration to growing or adult cats has been without effect. 8. Daily injections of parathormone in growing rats results in an increased number of trabeculae and smaller bones.
DNA methyltransferase 1 functions through C/ebpa to maintain hematopoietic stem and progenitor cells in zebrafish
Authors: Xiaohui Liu, Xiaoe Jia, Hao Yuan, Ke Ma, Yi Chen, Yi Jin, Min Deng, Weijun Pan, Saijuan Chen, Zhu Chen, Hugues de The, Leonard I Zon, Yi Zhou, Jun Zhou, Jun Zhu
Journal: Journal of Hematology & Oncology (2015)

DNA methyltransferase 1 (Dnmt1) regulates expression of many critical genes through maintaining parental DNA methylation patterns on daughter DNA strands during mitosis. It is essential for embryonic development and diverse biological processes, including maintenance of hematopoietic stem and progenitor cells (HSPCs). However, the precise molecular mechanism of how Dnmt1 is involved in HSPC maintenance remains unexplored. An N-ethyl-N-nitrosourea (ENU)-based genetic screening was performed to identify putative mutants with defects in definitive HSPCs during hematopoiesis in zebrafish. The expression of hematopoietic markers was analyzed via whole mount in situ hybridization assay (WISH). Positional cloning approach was carried out to identify the gene responsible for the defective definitive hematopoiesis in the mutants. Analyses of the mechanism were conducted by morpholino-mediated gene knockdown, mRNA injection rescue assays, anti-phosphorylated histone H3 (pH3) immunostaining and TUNEL assay, quantitative real-time PCR, and bisulfite sequencing analysis. A heritable mutant line with impaired HSPCs of definitive hematopoiesis was identified. Positional cloning demonstrated that a stop codon mutation was introduced in dnmt1 which resulted in a predicted truncated Dnmt1 lacking the DNA methylation catalytic domain. Molecular analysis revealed that expression of CCAAT/enhancer-binding protein alpha (C/ebpa) was upregulated, which correlated with hypomethylation of CpG islands in the regulation regions of cebpa gene in Dnmt1 deficient HSPCs. Overexpression of a transcriptional repressive SUMO-C/ebpa fusion protein could rescue hematological defects in the dnmt1 mutants. Finally, dnmt1 and cebpa double null embryos exhibited no obvious abnormal hematopoiesis indicated that the HSPC defects triggered by dnmt1 mutation were C/ebpa dependent. Dnmt1 is required for HSPC maintenance via cebpa regulation during definitive hematopoiesis in zebrafish.
Vo2 requirement at different displayed power outputs on five cycle ergometer models: a preliminary study
Authors: T Guiraud, L Léger, A Long, N Thébault, J Tremblay, P Passelergue
Journal: British Journal of Sports Medicine (2008)

Background and aims The validity of five brands of cycle ergometers was evaluated by the comparison of the Vo 2 requirements at different displayed power. Methods and results Five physically active men performed a continuous incremental exercise test on five ergometers (Ergomeca, Lifecycle, Monark, Polar S710 and CompuTrainer). The latter was also compared with a standard dynamometer in order to associate Vo 2 values with the real power. Every test started with a 5-min warm-up on the same cycle ergometer (Ergomeca) at 100 W to make sure that the Vo 2 differences do not come from Vo 2 measurement error. Only last minute steady-state Vo 2 values of each 2-min stage were used for the Vo 2 –watt curve. Large differences (5– 10 ml kg −1 min −1 ) at the same displayed power indicate inaccuracy of displayed power output (PO). Using corrected power values from the dynamometer revealed that for the same Vo 2 the CompuTrainer underestimates PO by ∼30 W between 100 and 300 W, whereas the Lifecycle overestimate it by 3–53 W from 100 to 300 W. The Monark and Polar S710 underestimate PO by 15 W and the Ergomeca by ∼5 W. Conclusion Inaccuracies between −10% and 18% in displayed PO of various cycle ergometers question their interchangeability.
DOES TYPE 1 DIABETES AFFECT ACHILLES TENDON RESPONSE TO A 10KM RUN?
Authors: A Wong, S Docking, J Cook, J Gaida
Journal: British Journal of Sports Medicine (2014)

Background Hyperglycaemia accelerates collagen cross-linking in tendons, which may manifest as an increased thickness or as an altered response to load. Type 1 diabetes mellitus (T1DM) is a unique population exhibiting hyperglycaemia independent of obesity and low physical activity. Ultrasound tissue characterisation (UTC) quantifies the structural integrity of a tendon based on the alignment of collagen, represented as echo-types (I-IV). Objective To measure achilles tendon response to a 10km run among individuals with T1DM and controls. Design In this case-control study, UTC scans were taken at day 0, 2, 4 after a 10 km run. Analysis of UTC scans was performed in a blinded fashion. Setting Social running club for people with T1DM. Participants Individuals with T1DM (n=7) were diagnosed 13±12 years ago. Control participants (n=10) had no diagnosis or family history of T1DM. Participants all regularly ran ≥5 km in a recreational capacity with an average weekly distance of 18±3 km. VISA-A scores were 94±11 (T1DM) and 94±10 (control). Risk factor assessment The independent variable was diagnosis of T1DM (yes/no). HbA1c and blood glucose were also measured. Main outcome measurements Tendon response to a 10km run measured with UTC was defined as the key outcome variable before data collection. Results Baseline structure was the same in control and T1DM groups for all UTC four echo-types (I-IV) and for anteroposterior thickness (P&gt;.05). Furthermore, no significant differences were observed within each group in response to the run. Conclusions A novel finding that Achilles tendon baseline structure and response to a 10 km run over 4-days is the same in controls and T1DM. This suggests that T1DM individuals who are regularly physically active do not undergo the same structural changes to their Achilles tendon as previously demonstrated in the general diabetic population.