tbuckley/cabot-search huggingface dataset:
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
Authors: Katleen De Preter, Jo Vandesompele, Pierre Heimann, Nurten Yigit, Siv Beckman, Alexander Schramm, Angelika Eggert, Raymond L Stallings, Yves Benoit, Marleen Renard, Anne De Paepe, Geneviève Laureys, Sven Påhlman, Frank Speleman
Journal: Genome biology (2006)

Abstract Background Neuroblastoma tumor cells are assumed to originate from primitive neuroblasts giving rise to the sympathetic nervous system. Because these precursor cells are not detectable in postnatal life, their transcription profile has remained inaccessible for comparative data mining strategies in neuroblastoma. This study provides the first genome-wide mRNA expression profile of these human fetal sympathetic neuroblasts. To this purpose, small islets of normal neuroblasts were isolated by laser microdissection from human fetal adrenal glands. Results Expression of catecholamine metabolism genes, and neuronal and neuroendocrine markers in the neuroblasts indicated that the proper cells were microdissected. The similarities in expression profile between normal neuroblasts and malignant neuroblastomas provided strong evidence for the neuroblast origin hypothesis of neuroblastoma. Next, supervised feature selection was used to identify the genes that are differentially expressed in normal neuroblasts versus neuroblastoma tumors. This approach efficiently sifted out genes previously reported in neuroblastoma expression profiling studies; most importantly, it also highlighted a series of genes and pathways previously not mentioned in neuroblastoma biology but that were assumed to be involved in neuroblastoma pathogenesis. Conclusion This unique dataset adds power to ongoing and future gene expression studies in neuroblastoma and will facilitate the identification of molecular targets for novel therapies. In addition, this neuroblast transcriptome resource could prove useful for the further study of human sympathoadrenal biogenesis.
Inhibition of Semaphorin As a Novel Strategy for Therapeutic Angiogenesis
Authors: Junji Moriya, Tohru Minamino, Kaoru Tateno, Sho Okada, Akiyoshi Uemura, Ippei Shimizu, Masataka Yokoyama, Aika Nojima, Mitsuhiro Okada, Hisashi Koga, Issei Komuro
Journal: Circulation Research (2009)

The axon-guiding molecules known as semaphorins and their receptors (plexins) regulate the vascular pattern and play an important role in the development of vascular network during embryogenesis. Semaphorin (Sema)3E is one of the class 3 semaphorins, and plexinD1 is known to be its receptor. Although these molecules have a role in embryonic vascular development, it remains unclear whether the Sema3E/plexinD1 axis is involved in postnatal angiogenesis.The objective of this study was to elucidate the role of Sema3E/plexinD1 in postnatal angiogenesis.Sema3E inhibited cell growth and tube formation by suppressing the vascular endothelial growth factor (VEGF) signaling pathway. Expression of Sema3E and plexinD1 was markedly upregulated in ischemic limbs of mice (2.5- and 4.5-fold increase for Sema3E and plexinD1, respectively), and inhibition of this pathway by introduction of the plexinD1-Fc gene or disruption of Sema3E led to a significant increase of blood flow recovery (1.6- and 1.5-fold increase for the plexinD1-Fc gene treatment and Sema3E disruption, respectively). Hypoxia activated the tumor suppressor protein p53, thereby upregulating Sema3E expression. Expression of p53 and Sema3E was enhanced in diabetic mice compared with normal mice (2- and 1.3-fold increase for p53 and Sema3E, respectively). Consequently, neovascularization after VEGF treatment was poor in the ischemic tissues of diabetic mice, whereas treatment with VEGF plus plexinD1-Fc markedly improved neovascularization.These results indicate that inhibition of Sema3E may be a novel strategy for therapeutic angiogenesis, especially when VEGF is ineffective.
ACUTE INJURIES IN 35 SPORTS; INCIDENCES AND SEVERITY
Authors: M Åman, K Henriksson-Larsén
Journal: British Journal of Sports Medicine (2014)

Background Acute injuries in sports are still a problem and the knowledge of incidences and severity in different sports at a national level are limited. Objective The aim of this study was to identify high-risk sports with respect to incidence of injury and severity of injuries in 35 sports. Design A retrospective cohort study was set up based on a comprehensive database from an insurance company. Setting Almost 90% of all athletes in Sweden (in 57/70 sports federations), in all ages and at all competitive levels, have their accident insurance in the same insurance company. Participants All licensed athletes in 35 sports during 2009–2011. Main outcome measurements The incidence of sport injuries as well as severe injuries (medical disability) were calculated for licensed athletes at a national level. Comparisons between sports, gender, and ages were made. Risk ratio was calculated with median injury incidence as the norm. Results Each year approximately 12 000 injuries (in total 35 971 injuries during 2009–2011) and 1 170 000 licensed athletes were eligible for analysis. The incidence of injury was higher in team sport compared to individual sports. Individual sports with highest incidence were motorcycle/snowmobile, skating, and wrestling. Team sports with highest incidence were handball, ice hockey, and rugby. Sports with a large number of injuries were soccer, ice hockey, floor ball, and handball. Highest proportions of medical disabilities were in motorcycle and then in team sports, such as soccer, basket, handball, and floor ball. Risk ratio for motorcycle was 15 and handball 14. Conclusions Sports with numerous acute injuries, high incidence and more severe injuries must be the target for prevention actions. This study suggests that team sports and motorcycle should be the object. Next step is to identify injury types, anatomical locations and injury mechanisms to understand how to prevent these injuries.
Volatile organic compounds in runners near a roadway: increased blood levels after short-duration exercise
Authors: C Blair, J Walls, N W Davies, G A Jacobson
Journal: British Journal of Sports Medicine (2008)

Objective To determine if non-elite athletes undertaking short duration running exercise adjacent to a busy roadway experience increased blood levels of common pollutant volatile organic compounds (benzene, toluene, ethylbenzene and xylene (BTEX)). Design and setting The study was observational in design. Participants (nine males/one female non-elite athletes) ran for 20 min, near a busy roadway along a 100 m defined course at their own pace. Blood levels of BTEX were determined both pre- and post-exercise by SPME-GC-MS. Environmental BTEX levels were determined by passive adsorption samplers. Results Subjects completed a mean (range) distance of 4.4 (3.4 to 5.2) km over 20 min (4.5 (3.8 to 5.9) min/km pace), with a mean (SD) exercise intensity of 93 (2.3)% HR max , and mean (SD) ventilation significantly elevated compared with resting levels (86.2 (2.3) vs 8.7 (0.9) l/min; p&lt;0.001). The mean (SD) environmental levels (time weighted average) were determined as 53.1 (4.2), 428 (83), and 80.0 (3.7) μg/m 3 for toluene, ethylbenzene and xylenes, respectively, while benzene was below the detectable limit due to the short exposure period. Significant increases in blood BTEX levels were observed in runners between pre- and postexercise for toluene (mean increase of 1.4 ng/ml; p=0.002), ethylbenzene (0.7 ng/ml; p=0.0003), m/p -xylene (2.0 ng/ml; p=0.004) and o -xylene (1.1 ng/ml; p=0.002), but no change was observed for benzene. Conclusions Blood BTEX levels are increased during high-intensity exercise such as running undertaken in areas with BTEX pollution, even with a short duration of exercise. This may have health implications for runners who regularly exercise near roadways.
Cyclooxygenase-2 Inhibits Novel Ginseng Metabolite-Mediated Apoptosis
Authors: Hyung Woo Yim, Hyun-Soon Jong, Tai Young Kim, Hyun Ho Choi, Sang Gyun Kim, Sang Hyun Song, Juyong Kim, Seong-Gyu Ko, Jung Weon Lee, Tae-You Kim, Yung-Jue Bang
Journal: Cancer Research (2005)

Recently, a novel intestinal bacterial metabolite of ginseng protopanaxadiol saponins, i.e., 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), has been reported to induce apoptosis in a variety of cancer cells. Here we show a differential effect of IH-901 on several cell types. Exposure to IH-901 for 48 hours at a supposedly subapoptotic concentration of 40 mumol/L led to both apoptotic cell death and G1 arrest in Hep3B cells, but only resulted in G1 arrest in MDA-MB-231, Hs578T, and MKN28 cells. Additionally, the treatment of MDA-MB-231, but not of Hep3B, with IH-901 up-regulated cyclooxygenase-2 (COX-2) mRNA (2 hours) and protein (6 hours), and enhanced the production of prostaglandin E2. In MDA-MB-231 cells, IH-901 induced the sustained activation of extracellular signal-regulated kinase (ERK), whereas inhibition of mitogen-activated protein/ERK kinase blocked IH-901-mediated COX-2 induction and resulted in apoptosis, suggesting the involvement of an ERK-COX-2 pathway. Combined treatment with IH-901 and nonsteroidal anti-inflammatory drugs inhibited COX-2 enzyme and induced apoptosis in MDA-MB-231 and Hs578T cells. Adenovirus-mediated COX-2 small interfering RNAs also effectively inhibited COX-2 protein expression and enhanced IH-901-mediated apoptosis without inhibiting ERK 1/2 phosphorylation, thus providing direct evidence that COX-2 is an antiapoptotic molecule. Moreover, IH-901-mediated G1 arrest resulted from an increase in p27Kip1 mRNA and protein expression followed by a decrease in CDK2 kinase activity that was concurrent with the hypophosphorylation of Rb and p130. In conclusion, IH-901 induced both G1 arrest and apoptosis, and this apoptosis could be inhibited by COX-2 induction.
Aprotinin impairs endothelium-dependent relaxation in rat aorta and inhibits nitric oxide release from rat coronary endothelial cells
Authors: S Ülker
Journal: Cardiovascular Research (2001)

Objective: Aprotinin, a non-specific serine protease inhibitor, reduces postoperative bleeding after coronary artery surgery. The mechanism of action for this ‘blood-sparing’ effect of aprotinin is only partially clarified. We therefore aimed to investigate the effect of aprotinin on the release of nitric oxide (NO), a vasodilator and antiaggregant factor, from rat coronary microvascular endothelial cells and on the NO-mediated endothelium-dependent relaxation of rat thoracic aorta. Methods: Endothelium-intact and endothelium-denuded thoracic aortic rings from Wistar rats (250–300 g) were suspended in organ chambers. Contractile and relaxant responses in the absence and presence of aprotinin (125, 250 and 500 KIU/ml) were recorded via a mechanotransducer. Coronary microvascular endothelial cells (CMEC) were isolated on a Langendorff system by collagenase perfusion of the hearts from the same rats. Calcium ionophore- (1 μM) induced release of NO from confluent cells was determined spectrophotometrically by measuring its stable metabolites, nitrite and nitrate, via Griess reaction. Results: Aprotinin selectively enhanced phenylephrine-induced contractions in endothelium-intact rat thoracic aortic rings, but not in the endothelium-denuded rings. The use of a nitric oxide synthesis inhibitor Nω-nitro-l-arginine methyl ester (100 μM) on endothelium-intact rings produced a similar increase in phenylephrine-induced contractions. KCl-induced contractions remained unaltered. Aprotinin inhibited acetylcholine-, calcium ionophore- and l-arginine-induced endothelium-dependent relaxations, but not sodium nitroprusside-induced endothelium-independent relaxation. Aprotinin had no significant effect on basal nitrite–nitrate release from CMEC, while it inhibited calcium ionophore-induced total nitrite accumulation in the supernatants. Conclusion: Aprotinin selectively impairs endothelium-dependent relaxation as well as basal NO availability in rat thoracic aortic rings and inhibits NO release from rat CMEC. This effect of the drug may contribute to its ‘blood-sparing’ action and may also account for the increase in perioperative restenosis risk observed in clinical practice during aprotinin therapy.
Surgical Treatment of Moderate Ischemic Mitral Regurgitation
Authors: Peter K. Smith, John D. Puskas, Deborah D. Ascheim, Pierre Voisine, Annetine C. Gelijns, Alan J. Moskowitz, Judy W. Hung, Michael K. Parides, Gorav Ailawadi, Louis P. Perrault, Michael A. Acker, Michael Argenziano, Vinod Thourani, James S. Gammie, Marissa A. Miller, Pierre Pagé, Jessica R. Overbey, Emilia Bagiella, François Dagenais, Eugene H. Blackstone, Irving L. Kron, Daniel J. Goldstein, Eric A. Rose, Ellen G. Moquete, Neal Jeffries, Timothy J. Gardner, Patrick T. O'Gara, John H. Alexander, Robert E. Michler
Journal: New England Journal of Medicine (2014)

Ischemic mitral regurgitation is associated with increased mortality and morbidity. For surgical patients with moderate regurgitation, the benefits of adding mitral-valve repair to coronary-artery bypass grafting (CABG) are uncertain.
Common Familial Colorectal Cancer Linked to Chromosome 7q31: A Genome-Wide Analysis
Authors: Deborah W. Neklason, Richard A. Kerber, David B. Nilson, Hoda Anton-Culver, Ann G. Schwartz, Constance A. Griffin, Jan T. Lowery, Joellen M. Schildkraut, James P. Evans, Gail E. Tomlinson, Louise C. Strong, Alexander R. Miller, Jill E. Stopfer, Dianne M. Finkelstein, Prakash M. Nadkarni, Carol H. Kasten, Geraldine P. Mineau, Randall W. Burt
Journal: Cancer Research (2008)

Abstract Present investigations suggest that ∼30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores ≥2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (± 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21–q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer. [Cancer Res 2008;68(21):8993–7]
Niche displacement of human leukemic stem cells uniquely allows their competitive replacement with healthy HSPCs
Authors: Allison L. Boyd, Clinton J.V. Campbell, Claudia I. Hopkins, Aline Fiebig-Comyn, Jennifer Russell, Jelena Ulemek, Ronan Foley, Brian Leber, Anargyros Xenocostas, Tony J. Collins, Mickie Bhatia
Journal: The Journal of Experimental Medicine (2014)

Allogeneic hematopoietic stem cell (HSC) transplantation (HSCT) is currently the leading strategy to manage acute myeloid leukemia (AML). However, treatment-related morbidity limits the patient generalizability of HSCT use, and the survival of leukemic stem cells (LSCs) within protective areas of the bone marrow (BM) continues to lead to high relapse rates. Despite growing appreciation for the significance of the LSC microenvironment, it has remained unresolved whether LSCs preferentially situate within normal HSC niches or whether their niche requirements are more promiscuous. Here, we provide functional evidence that the spatial localization of phenotypically primitive human AML cells is restricted to niche elements shared with their normal counterparts, and that their intrinsic ability to initiate and retain occupancy of these niches can be rivaled by healthy hematopoietic stem and progenitor cells (HSPCs). When challenged in competitive BM repopulation assays, primary human leukemia-initiating cells (L-ICs) can be consistently outperformed by HSPCs for BM niche occupancy in a cell dose-dependent manner that ultimately compromises long-term L-IC renewal and subsequent leukemia-initiating capacity. The effectiveness of this approach could be demonstrated using cytokine-induced mobilization of established leukemia from the BM that facilitated the replacement of BM niches with transplanted HSPCs. These findings identify a functional vulnerability of primitive leukemia cells, and suggest that clinical development of these novel transplantation techniques should focus on the dissociation of L-IC–niche interactions to improve competitive replacement with healthy HSPCs during HSCT toward increased survival of patients.
A Non-T, Non-B Human Leukemia Cell Line (NALM-1): Establishment of the Cell Line and Presence of Leukemia-Associated Antigens2
Authors: J. Minowada, T. Tsubota, M. F. Greaves, T. R. Walters
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article A Non-T, Non-B Human Leukemia Cell Line (NALM-1): Establishment of the Cell Line and Presence of Leukemia-Associated Antigens Get access J. Minowada, J. Minowada Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Tsubota, T. Tsubota Search for other works by this author on: Oxford Academic PubMed Google Scholar M. F. Greaves, M. F. Greaves Search for other works by this author on: Oxford Academic PubMed Google Scholar T. R. Walters T. R. Walters Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 1, July 1977, Pages 83–87, https://doi.org/10.1093/jnci/59.1.83 Published: 01 July 1977 Article history Received: 11 November 1976 Accepted: 25 January 1977 Published: 01 July 1977
ACNE IN AN INFANT
Authors: WALLACE BEATTY, JOSEPH W. BIGGER
Journal: British Journal of Dermatology (1923)

Journal Article ACNE IN AN INFANT Get access WALLACE BEATTY, M.D., WALLACE BEATTY, M.D. Search for other works by this author on: Oxford Academic Google Scholar JOSEPH W. BIGGER, M.D. JOSEPH W. BIGGER, M.D. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 35, Issue 8-9, 1 August 1923, Pages 325–326, https://doi.org/10.1111/j.1365-2133.1923.tb09123.x Published: 01 August 1923
Change in the discontinuation pattern of tumour necrosis factor antagonists in rheumatoid arthritis over 10 years: data from the Spanish registry BIOBADASER 2.0
Authors: Juan J Gómez-Reino, Carlos Rodríguez-Lozano, Cristina Campos-Fernández, María Montoro, Miguel Ángel Descalzo, Loreto Carmona
Journal: Annals of the Rheumatic Diseases (2011)

To investigate in rheumatoid arthritis (RA) the rate and reason of discontinuation of tumour necrosis factor (TNF) antagonists over the past decade.RA patients in BIOBADASER 2.0 were stratified according to the start date of their first TNF antagonist into 2000-3, 2004-6 and 2007-9 interval years. Cumulative incidence function of discontinuation for inefficacy or toxicity was estimated with the alternative reason as competing risk. Competing risks regression models were used to measure the association of study groups with covariates and reasons for discontinuation. Association is expressed as subhazard ratios (SHR).2907 RA patients were included in the study. Competing risk regression for inefficacy shows larger SHR for patients starting treatment in 2004-6 (SHR 2.57; 95% CI 1.55 to 4.25) and 2007-9 (SHR 3.4; 95% CI 2.08 to 5.55) than for those starting in 2000-3, after adjusting for TNF antagonists, clinical activity and concomitant treatment. Competing risk regression analysis for adverse events revealed no differences across the three time intervals.In RA, the discontinuation rate of TNF antagonists in the first year of treatment is higher more recently than a decade ago, inefficacy being the main reason for the increased rate. The rate of discontinuation for adverse events has remained stable.
Reply to K.A. Olaussen et al
Authors: Li-E Wang, Christopher I. Amos, Margaret R. Spitz, Qingyi Wei
Journal: Journal of Clinical Oncology (2012)

related to an increase in dose-intensity and thus higher clinical efficacy that is unrelated to higher tumor sensitivity, and decreased chemotherapy-related mortality.Briefly, the excellent article from Wang et al 1 merits a few questions: Which cisplatin dose-intensity was delivered to the patients, and is this related to specific DRC levels?How many deaths were unrelated to cancer?Were disease-free survival and overall survival two comparable parameters in the studied patients?Did response rates correlate with lymphocyte DRC in patients with stage IV disease?Which parameters (other than sex, age, and smoking status) affected lymphocyte DRC (hereditary genetic background, tumor stage [not only separated according to resectable v nonresectable disease], previous treatments, and environment)?This functional test could potentially be evaluated to predict efficacy of alkylating agents in other tumor types (ie, cyclophosphamide in breast cancer).Furthermore, this test could potentially be used to predict toxicity, even in the adjuvant setting.
Role of nitric oxide, cyclic GMP and superoxide in inhibition by adenosine of calcium current in rabbit atrioventricular nodal cells
Authors: A Martynyuk
Journal: Cardiovascular Research (1997)

Objective: To study the intracellular pathways which mediate the inhibitory actions of adenosine on isoprenaline-stimulated calcium current (ICa) in atrioventricular (AV) nodal myocytes. Methods: The whole-cell patch-clamp technique was used to record ICa from rabbit AV nodal cells, isolated by enzymatic and mechanical dispersion. Results: Isoprenaline, 0.1 μM, increased peak ICa from 0.58±0.08 to 1.23±0.1 nA, and this increase was reversibly inhibited by adenosine, 10 μM (83±6%), which we have previously shown to be mediated by nitric oxide (NO) production. A membrane-permeable analogue of cyclic GMP, 8-Br-cGMP (300 μM), an inhibitor of cGMP-stimulated phosphodiesterase, prevented the effect of adenosine on ICa. Methylene blue (10 μM), an inhibitor of NO-sensitive guanylyl cyclase and a generator of superoxide (·O2−), did not prevent, but increased, the inhibiting action of adenosine (49.5±6.6%, P<0.01). Methylene blue (50 μM) caused a reduction of ICa, with further inhibition when combined with adenosine. A ·O2−-generating system, xanthine oxidase (0.02 U/ml) and purine (2.3 mM), also increased the inhibitory action of adenosine on ICa. Inhibition of ICa by adenosine in the presence of xanthine oxidase was not prevented by 8-Br-cGMP (300 μM) and was not influenced by pre-incubation of cells with a NO synthase inhibitor, l-NAME (0.5 mM). Conclusions: The inhibitory effect of adenosine on ICa in rabbit AV nodal myocytes can be mediated by two mechanisms—stimulation of cGMP-stimulated phosphodiesterase by NO-induced cGMP, and a mechanism which involves interaction with ·O2− production.