tbuckley/cabot-search huggingface dataset:
Non-hematopoietic cells contribute to protective tolerance to Aspergillus fumigatus via a TRIF pathway converging on IDO
Authors: Antonella de Luca, Silvia Bozza, Teresa Zelante, Silvia Zagarella, Carmen D'Angelo, Katia Perruccio, Carmine Vacca, Agostinho Carvalho, Cristina Cunha, Franco Aversa, Luigina Romani
Journal: Cellular and Molecular Immunology (2010)
IDH1/2 mutations target a key hallmark of cancer by deregulating cellular metabolism in glioma
Authors: Chunzhi Zhang, Lynette M. Moore, Xia Li, W. K. Alfred Yung, Wei Zhang
Journal: Neuro-Oncology (2013)

Isocitrate dehydrogenase (IDH) enzymes have recently become a focal point for research aimed at understanding the biology of glioma. IDH1 and IDH2 are mutated in 50%–80% of astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary glioblastomas but are seldom mutated in primary glioblastomas. Gliomas with IDH1/2 mutations always harbor other molecular aberrations, such as TP53 mutation or 1p/19q loss. IDH1 and IDH2 mutations may serve as prognostic factors because patients with an IDH-mutated glioma survive significantly longer than those with an IDH–wild-type tumor. However, the molecular pathogenic role of IDH1/2 mutations in the development of gliomas is unclear. The production of 2-hydroxyglutarate and enhanced NADP+ levels in tumor cells with mutant IDH1/2 suggest mechanisms through which these mutations contribute to tumorigenesis. Elucidating the pathogenesis of IDH mutations will improve understanding of the molecular mechanisms of gliomagenesis and may lead to development of a new molecular classification system and novel therapies.
Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse
Authors: M R Graham, F M Grace, W Boobier, D Hullin, A Kicman, D Cowan, B Davies, J S Baker
Journal: British Journal of Sports Medicine (2006)

The long term effects (>20 years) of anabolic-androgenic steroid (AAS) use on plasma concentrations of homocysteine (HCY), folate, testosterone, sex hormone binding globulin (SHBG), free androgen index, urea, creatinine, haematocrit (HCT), vitamin B12, and urinary testosterone/epitestosterone (T/E) ratio, were examined in a cohort of self-prescribing bodybuilders.Subjects (n = 40) were divided into four distinct groups: (1) AAS users still using AAS (SU; n = 10); (2) AAS users abstinent from AAS administration for 3 months (SA; n = 10); (3) non-drug using bodybuilding controls (BC; n = 10); and (4) sedentary male controls (SC; n = 10).HCY levels were significantly higher in SU compared with BC and SC (p<0.01), and with SA (p<0.05). Fat free mass was significantly higher in both groups of AAS users (p<0.01). Daily energy intake (kJ) and daily protein intake (g/day) were significantly higher in SU and SA (p<0.05) compared with BC and SC, but were unlikely to be responsible for the observed HCY increases. HCT concentrations were significantly higher in the SU group (p<0.01). A significant linear inverse relationship was observed in the SU group between SHBG and HCY (r = -0.828, p<0.01), indicating a possible influence of the sex hormones in determining HCY levels.With mounting evidence linking AAS to adverse effects on some clotting factors, the significantly higher levels of HCY and HCT observed in the SU group suggest long term AAS users have increased risk of future thromboembolic events.
Physicochemical Foundations and Structural Design of Hydrogels in Medicine and Biology
Authors: N. A. Peppas, Y. Huang, M. Torres-Lugo, J. H. Ward, J. Zhang
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.
The Coamplification Pattern of the <i>MYCN</i> Amplicon Is an Invariable Attribute of Most <i>MYCN</i>-Amplified Human Neuroblastomas
Authors: Axel Weber, Sven Starke, Eckhard Bergmann, Holger Christiansen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Fifteen percent to 20% of human neuroblastomas show amplification of the MYCN oncogene physiologically located at chromosome 2p24-25, indicating an aggressive subtype of human neuroblastoma with a poor clinical outcome. Recent findings revealed that the structure of the amplicon differs interindividually and that coamplification of genes in telomeric proximity to MYCN might play a relevant role in neuroblastoma development and response to treatment, respectively. We now asked if the amplicon structure is an invariable attribute of an individual tumor or if the coamplification pattern could change during progress or in case of recurrent disease. Experimental Design: We used a previously described multiplex PCR approach to analyze the coamplification status of MYCN-amplified human neuroblastomas (n = 33) in tumor tissue at the time of initial diagnosis and in consecutive tissue specimens at later time points after initial treatment or from relapsing disease. The MYCN copy number per haploid genome (Mcn/hg) in these specimens was determined in a separate duplex PCR. Results: In 32 of the 33 investigated tumors, the amplicon structure showed no changes after initial chemotherapy and in recurrent disease. Mcn/hg showed a decrease after initial treatment (n = 23), whereas we found a significant increase in recurrent disease (n = 10). Conclusion: Our data indicate that the initial determined structure of the 2p24-25 amplicon is a consistent attribute in the great majority of the individual MYCN-amplified neuroblastomas and shows no plasticity during or after chemotherapy. Observed changes in the Mcn/hg over the course of disease are in line with preexisting cell culture findings.
Global expression analysis of the brown alga Ectocarpus siliculosus (Phaeophyceae) reveals large-scale reprogramming of the transcriptome in response to abiotic stress
Authors: Simon M Dittami, Delphine Scornet, Jean-Louis Petit, Béatrice Ségurens, Corinne Da Silva, Erwan Corre, Michael Dondrup, Karl-Heinz Glatting, Rainer König, Lieven Sterck, Pierre Rouzé, Yves Van de Peer, J Mark Cock, Catherine Boyen, Thierry Tonon
Journal: Genome biology (2009)

Brown algae (Phaeophyceae) are phylogenetically distant from red and green algae and an important component of the coastal ecosystem. They have developed unique mechanisms that allow them to inhabit the intertidal zone, an environment with high levels of abiotic stress. Ectocarpus siliculosus is being established as a genetic and genomic model for the brown algal lineage, but little is known about its response to abiotic stress. Here we examine the transcriptomic changes that occur during the short-term acclimation of E. siliculosus to three different abiotic stress conditions (hyposaline, hypersaline and oxidative stress). Our results show that almost 70% of the expressed genes are regulated in response to at least one of these stressors. Although there are several common elements with terrestrial plants, such as repression of growth-related genes, switching from primary production to protein and nutrient recycling processes, and induction of genes involved in vesicular trafficking, many of the stress-regulated genes are either not known to respond to stress in other organisms or are have been found exclusively in E. siliculosus. This first large-scale transcriptomic study of a brown alga demonstrates that, unlike terrestrial plants, E. siliculosus undergoes extensive reprogramming of its transcriptome during the acclimation to mild abiotic stress. We identify several new genes and pathways with a putative function in the stress response and thus pave the way for more detailed investigations of the mechanisms underlying the stress tolerance ofbrown algae.
Expression of laminin α2 chain during normal and pathological growth of myocardium in rat and human
Authors: Patricia Oliviéro, Catherine Chassagne, Nathalie Salichon, Alain Corbier, Gilles Hamon, Françoise Marotte, Danièle Charlemagne, Lydie Rappaport, Jane-Lise Samuel
Journal: Cardiovascular Research (2000)

Fibrosis is a classical feature of cardiac hypertrophy. To date changes within the basal lamina during normal and pathological cardiac growth have been poorly investigated. The goal of the present study was to determine if the expression of the muscle specific subunit of merosin (laminin alpha2 chain) together with that of fibronectin (FN) is modified in the diseased human heart. Laminin alpha2 chain expression was also investigated during physiological and pathological cardiac growth in the rat.In ten normal human hearts and ten hearts with idiopathic dilated cardiomyopathy (IDCM), the laminin-alpha2 and FN mRNA levels were quantified by slot-blot using total RNA and the protein distribution was analysed using an immunofluorescence approach. In Wistar rats, laminin alpha2 and FN mRNA expression was analyzed using RNase protection assay (RPA) and slot-blot assays.The amount of laminin alpha2 mRNA did not vary in normal and pathological human hearts whereas it was significantly decreased in renovascular hypertensive rats (-20%) P<0.05 versus normal tissue). The amount of fibronectin mRNA increased in IDMC patients (x2, P<0.05 versus normal tissue), but was unchanged in hypertensive rats. A negative correlation was found between the cardiac laminin-alpha2 level and the age of the patients whatever the cardiac status. During postnatal development in the rat, a similar decrease in cardiac laminin-alpha2 level was observed between 3 and 30 weeks of age. Finally, the immunofluorescent approach failed to detect any alteration in laminin alpha2 distribution within the human myocardium.These data indicate that an imbalance between myocyte hypertrophy and the level of laminin-alpha2 might contribute to alterations in sarcolemmal properties, which occur during the development of cardiac hypertrophy and its transition to cardiac failure.
Fluid loss among swimmers during different duration water workouts
Authors: Sapna Aggarwal
Journal: British Journal of Sports Medicine (2010)

To compare the amount of fluid lost among swimmers during different duration water workouts, 15 swimmers (10 males and 5 females) with age ranging from 17 to 23 with a mean and SD of 20.13 ± 2.06 years were selected randomly from LNIPE Swimming group. The subjects were given three treatments, that is, 12, 18 and 24 min continuous swimming. The data were collected under similar conditions on three different days with 2 days rest in between each treatment for full recovery. In order to measure amount of body fluid loss in swimmers ‘Wintrobe Test’ was used. The difference between the pre- and post blood samples was expressed in terms of number of plasma content, white blood cells and red blood cell. There was no significant difference found in the mean body fluid lost in three treatments given to swimmers. Value of calculated ‘f’, that is, 3.35 was less than the tabulated ‘f’, that is, 19.47 at the 0.05 level of significance. It shows that there was no variability of the amount of fluid loss during different durations of water workouts which is statistically insignificant.
Euthanasia, Ethics and Public Policy: An Argument Against Legalisation
Authors: T. Sheldon
Journal: BMJ (2003)

One exasperated Amsterdam general practitioner recently said to me: “Do we know enough about subcutaneous morphine? The [euthanasia] law demands we investigate all reasonable alternatives.” John Keown Cambridge University Press, £16.95, pp 338 ISBN 0 521 00933 2 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> This remark illustrates how Dutch doctors, working in the first society in the world that has effectively decriminalised mercy killing, are concerned about practising at the frontiers of medical ethics. But not concerned enough for John Keown, senior lecturer in the law and ethics of medicine at … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Renal Vein Levels of MicroRNA-26a Are Lower in the Poststenotic Kidney
Authors: Xiang-Yang Zhu, Behzad Ebrahimi, Alfonso Eirin, John R. Woollard, Hui Tang, Kyra L. Jordan, Michael Ofori, Ahmed Saad, Sandra M.S. Herrmann, Allan B. Dietz, Stephen C. Textor, Amir Lerman, Lilach O. Lerman
Journal: Journal of the American Society of Nephrology (2014)

MicroRNA-26a (miR-26a) is a post-transcriptional regulator that inhibits cellular differentiation and apoptosis. Renal vascular disease (RVD) induces ischemic injury characterized by tubular cell apoptosis and interstitial fibrosis. We hypothesized that miR-26a levels are reduced in the poststenotic kidney and that kidney repair achieved by adipose tissue-derived mesenchymal stem cells (ad-MSCs) is associated with restored miR-26a levels. Renal function and renal miR-26a levels were assessed in pigs with RVD not treated (n=7) or 4 weeks after intrarenal infusion of ad-MSC (2.5×10(5) cells/kg; n=6), patients with RVD (n=12) or essential hypertension (n=12), and healthy volunteers (n=12). In addition, the direct effect of miR-26a on apoptosis was evaluated in a renal tubular cell culture. Compared with healthy control kidneys, swine and human poststenotic kidneys had 45.5±4.3% and 90.0±3.5% lower levels of miR-26a, respectively, which in pigs, localized to the proximal tubules. In pigs, ad-MSC delivery restored tubular miR-26a expression, attenuated tubular apoptosis and interstitial fibrosis, and improved renal function and tubular oxygen-dependent function. In vitro, miR-26a inhibition induced proximal tubular cell apoptosis and upregulated proapoptotic protein expression, which were both rescued by ad-MSC. In conclusion, decreased tubular miR-26a expression in the poststenotic kidney may be responsible for tubular cell apoptosis and renal dysfunction but can be restored using ad-MSC. Therefore, miR-26a might be a novel therapeutic target in renovascular disease.
Osteogenesis Associates With Inflammation in Early-Stage Atherosclerosis Evaluated by Molecular Imaging In Vivo
Authors: Elena Aikawa, Matthias Nahrendorf, Jose-Luiz Figueiredo, Filip K. Swirski, Timur Shtatland, Rainer H. Kohler, Farouc A. Jaffer, Masanori Aikawa, Ralph Weissleder
Journal: Circulation (2007)

Background— Arterial calcification is associated with cardiovascular events; however, mechanisms of calcification in atherosclerosis remain obscure. Methods and Results— We tested the hypothesis that inflammation promotes osteogenesis in atherosclerotic plaques using in vivo molecular imaging in apolipoprotein E −/− mice (20 to 30 weeks old, n=35). A bisphosphonate-derivatized near-infrared fluorescent imaging agent (excitation 750 nm) visualized osteogenic activity that was otherwise undetectable by x-ray computed tomography. Flow cytometry validated the target specifically in osteoblast-like cells. A spectrally distinct near-infrared fluorescent nanoparticle (excitation 680 nm) was coinjected to simultaneously image macrophages. Fluorescence reflectance mapping demonstrated an association between osteogenic activity and macrophages in aortas of apolipoprotein E −/− mice ( R 2 =0.93). Intravital dual-channel fluorescence microscopy was used to further monitor osteogenic changes in inflamed carotid arteries at 20 and 30 weeks of age and revealed that macrophage burden and osteogenesis concomitantly increased during plaque progression ( P &lt;0.01 and P &lt;0.001, respectively) and decreased after statin treatment ( P &lt;0.0001 and P &lt;0.05, respectively). Fluorescence microscopy on cryosections colocalized near-infrared fluorescent osteogenic signals with alkaline phosphatase activity, bone-regulating protein expression, and hydroxyapatite nanocrystals as detected by electron microscopy, whereas von Kossa and alizarin red stains showed no evidence of calcification. Real-time reverse-transcription polymerase chain reaction revealed that macrophage-conditioned media increased alkaline phosphatase mRNA expression in vascular smooth muscle cells. Conclusions— This serial in vivo study demonstrates the real-time association of macrophage burden with osteogenic activity in early-stage atherosclerosis and offers a cellular-resolution tool to identify preclinical microcalcifications.
Duodenal bulb plasma cells in duodenitis and duodenal ulceration.
Authors: B B Scott, A Goodall, P Stephenson, D Jenkins
Journal: Gut (1985)

Using an immunoperoxidase technique IgA, IgM, IgE and IgG plasma cells were studied in endoscopic duodenal bulb biopsies taken from 14 controls, 25 patients with grade 1 duodenitis (Whitehead classification), 12 patients with grade 2 duodenitis and three with grade 3 duodenitis. The control counts were compared with those in the jejunum and rectum. In addition cell counts were compared in 16 pairs of patients, with and without duodenal ulcer, exactly matched for grade of duodenitis. The control counts were not significantly different from counts in jejunum or rectum except for IgG which were higher in the jejunum (p = 0.03). IgA plasma cell counts were significantly increased in both grade 1 and grade 2 duodenitis compared with controls (p less than 0.05 and p less than 0.01). There was no significant difference for the other plasma cells. All plasma cell counts were decreased in the small group of grade 3 duodenitis compared with the other groups. There was no significant difference between counts in duodenitis whether or not there was associated duodenal ulceration. The isolated IgA plasma cell response of the duodenal bulb mucosa in duodenitis is very different from that of the jejunal mucosa in coeliac disease, and the rectal mucosa in inflammatory bowel disease and bacterial colitis and probably represents the basic response to any mucosal damage.
Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans
Authors: Samir M Parikh, Tadanori Mammoto, Aylit Schultz, Hai-Tao Yuan, David Christiani, S. Ananth Karumanchi, Vikas P Sukhatme
Journal: PLoS Medicine (2006)

Acute respiratory distress syndrome (ARDS) is a devastating complication of numerous underlying conditions, most notably sepsis. Although pathologic vascular leak has been implicated in the pathogenesis of ARDS and sepsis-associated lung injury, the mechanisms promoting leak are incompletely understood. Angiopoietin-2 (Ang-2), a known antagonist of the endothelial Tie-2 receptor, was originally described as a naturally occurring disruptor of normal embryonic vascular development otherwise mediated by the Tie-2 agonist angiopoietin-1 (Ang-1). We hypothesized that Ang-2 contributes to endothelial barrier disruption in sepsis-associated lung injury, a condition involving the mature vasculature.We describe complementary human, murine, and in vitro investigations that implicate Ang-2 as a mediator of this process. We show that circulating Ang-2 is significantly elevated in humans with sepsis who have impaired oxygenation. We then show that serum from these patients disrupts endothelial architecture. This effect of sepsis serum from humans correlates with measured Ang-2, abates with clinical improvement, and is reversed by Ang-1. Next, we found that endothelial barrier disruption can be provoked by Ang-2 alone. This signal is transduced through myosin light chain phosphorylation. Last, we show that excess systemic Ang-2 provokes pulmonary leak and congestion in otherwise healthy adult mice.Our results identify a critical role for Ang-2 in disrupting normal pulmonary endothelial function.
Preventing Obesity in Children and Adolescents
Authors: William H. Dietz, Steven L. Gortmaker
Journal: Annual Review of Public Health (2001)

▪ Abstract In this review, we address the natural history of obesity in children, the most promising family- and school-based approaches to the prevention of obesity, and the barriers and opportunities associated with secondary prevention. In childhood, the most important periods of risk appear to be the periods of adiposity rebound and adolescence. Caution regarding the period of adiposity rebound is still warranted, because it is not yet clear that early rebound is attributable to changes in body fat. Families and schools represent the most important foci for preventive efforts in children and adolescents. One productive approach is to proceed from an examination of factors that affect energy balance to the identification of more proximal influences on those factors. This approach may help to narrow the strategies necessary to prevent or treat childhood obesity. For example, television viewing affects both energy intake and energy expenditure, and therefore represents a logical target for interventions. Anticipatory guidance by pediatricians may offer an effective mechanism by which to change parental attitudes and practices regarding television viewing. A similar process is used to emphasize the potential influence of school-based interventions directed at changes in food choices and sedentary behavior.
Investigation of asthma prevalence in the adolescents of Russian Federation
Authors: Julia Levina, Leyla Namazova-Baranova, Raisa Torshkhoyeva, Elena Vishneva, Anna Tomilova, Ludmila Ogorodova, Ivan Deev, Kamilla Efendieva
Journal: European Respiratory Journal (2011)

Aim:  To definite the true prevalence of bronchial asthma (BA) in population of adolescents of Russian Federation.   Methods:  At the first stage, according to GA 2 LEN protocol, in 2 research centers (Moscow and Tomsk) a continuous sample of adolescents 15- 18 y.o. from own databases has been created. 12803 teenagers (5000 – Moscow, 7803 - Tomsk) have received the invitation to participate in research by post. Data of 2490 teenagers were included in statistical processing (19,5%: 1480 respondents from Moscow and 1010 from Tomsk). The average age of patients was 15,48±0,02 years.   Results:  Cumulative morbidity of BA was marked at 19,9% of all respondents included in research. The analysis of prevalence of clinically diagnosed BA has shown that only 7,2% of teenagers had medical-verified diagnosis (in 2,7 times less in comparison with the cumulative morbidity of asthma). During the complex examination of the select number of adolescents at the second stage of the study the diagnosis of asthma was verified at 5,7% of children from the group with astma-like symptoms and at 4,9% of children without asthma symptoms according to answers in questionnaires (average index was 5,1% of adolescents in group). According to the official data asthma morbidity makes 2836,25 o/oooo. Thus, true prevalence of asthma has appeared to be 4 times less then the prevalence of symptoms registered by patients, in 1,4 times less than “diagnosed illness” according to answers of patients and in 2 times above the data of official statistics.   Conclusions:  Use of the standardized indices, with the further clinical screening and complex examination allows to establish true prevalence of allergic diseases.