tbuckley/cabot-search huggingface dataset:
RNASEN Regulates Cell Proliferation and Affects Survival in Esophageal Cancer Patients
Authors: Nobuyoshi Sugito, Hideyuki Ishiguro, Yoshiyuki Kuwabara, Masahiro Kimura, Akira Mitsui, Hiroki Kurehara, Takuya Ando, Ryota Mori, Nobuhiro Takashima, Ryo Ogawa, Yoshitaka Fujii
Journal: Clinical Cancer Research (2006)

MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of some cancers. We studied the expression level of the miRNA processing enzyme (DICER1, DGCR8, and RNASEN) in esophageal squamous cell carcinoma (ESCC).The expression levels of DICER1, DGCR8, and RNASEN mRNA in 73 ESCC tissues were compared with that in corresponding normal esophageal epithelium by Taqman real-time reverse-transcription PCR. We also examined RNASEN protein expression in 27 cell lines. The role of RNASEN in cell proliferation in ESCC cells was assessed by small interfering RNA. Paraffin sections of ESCC patients were immunohistochemically investigated.We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. Multivariate Cox regression analysis showed that the prognostic effect of RNASEN (P = 0.0036) seems to be independent of disease stage (P = 0.0060). Knockdown of RNASEN in esophageal cancer cell lines resulted in a 46% to 85% reduction in cell number. In an immunohistochemical study, the intensity of RNASEN expression was often increased in the tumor compared with that in normal epithelium.The relationship between the RNASEN expression and the prognosis of the ESCC patients warrants a further study on the role of miRNA and tumor progression.
Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure
Authors: A J Ellis, R D Hughes, J A Wendon, J Dunne, P G Langley, J H Kelly, G T Gislason, N L Sussman, R Williams
Journal: Hepatology (1996)

The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty–four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3–168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD–treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD– treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot–controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.
A novel subset of CD4+ TH2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma
Authors: Yui-Hsi Wang, Kui Shin Voo, Bo Liu, Chun-Yu Chen, Burcin Uygungil, William Spoede, Jonathan A. Bernstein, David P. Huston, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (2010)

The inflammatory cytokine interleukin (IL)-17 is involved in the pathogenesis of allergic diseases. However, the identity and functions of IL-17–producing T cells during the pathogenesis of allergic diseases remain unclear. Here, we report a novel subset of TH2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce TH17 and TH2 cytokines. Classical TH2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokines IL-1β, IL-6, and IL-21. The number of IL-17-TH2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17–producing CD4+ TH2 cells were induced in the inflamed lung and persisted as the dominant IL-17–producing T cell population during the chronic stage of asthma. Treating cultured bronchial epithelial cells with IL-17 plus TH2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical TH17 and TH2 cells, antigen-specific IL-17–producing TH2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of TH2 memory cells and suggest that IL-17–producing TH2 cells may represent the key pathogenic TH2 cells promoting the exacerbation of allergic asthma.
EVALUATION OF THE PREVALENCE, KNOWLEDGE AND ATTITUDES RELATING TO β-ALANINE USE AMONG ATHLETES
Authors: VG Kelly, DG Jenkins, MD Leveritt, CT Brennan, GJ Slater
Journal: British Journal of Sports Medicine (2013)

β-alanine is an amino acid involved in the synthesis of carnosine, an intramuscular compound that buffers pH and has been associated with improvements in high intensity exercise performance. Little is currently known about the supplementation habits of β-alanine in professional athletes. The aim of this study was to investigate β-alanine supplementation use amongst professional athletes. Surveys assessing β-alanine practices beliefs and sources of information were completed by 570 professional footballers from Super Rugby (SR), Rugby League (NRL) and Australian Rules Football (AFL) in Australia. Approximately 61% of athletes reported β-alanine use, but use by AFL players was below that of SR and NRL. 90% of respondents had misconceptions on β-alanine's use, or were not using β-alanine in accordance with recommendations. Up to 60% of users experienced paraesthesia symptoms from β-alanine use and 70% of users sourced their information from strength and conditioning coaches, dietitians (∼50%), trainers(∼25%), and/or sport scientists (∼15%). Compared to NRL and AFL players, SR players had both a greater knowledge of β-alanine supplementation and better supplementation practices. This survey data of Australian professional football athletes indicates that, despite over half the athlete population using β-alanine, the majority of athletes had misconceptions relating to its use.
Reply to K. Satharasinghe et al
Authors: Brian H. Kushner, Kim Kramer, Shakeel Modak, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2009)

In our report, we did not discuss how relapses were documented— we assumed it would be self-evident that they must be confirmed unequivocably before salvage therapy is initiated. Satharasinghe et al raise concern about the 27% of patients whose relapse was detected only by iodine-123 (I) metaiodobenzylguanidine (MIBG) scan. Among those 25 patients, 24 had abnormal radiotracer uptake in one or more osteomedullary sites and one patient had new uptake in a small postoperative paraspinal site. Relapse was deemed unequivocal when multiple skeletal sites of abnormal MIBG uptake were present (n 7). In contrast, with a single new abnormal MIBG-avid osteomedullary site (n 17), the finding was judged as indicative of relapse only after magnetic resonance imaging revealed a corresponding lesion and follow-up MIBG scan remained abnormal (by which time other staging studies often also showed new disease). The paraspinal relapse was confirmed by disease resection after follow-up I-MIBG scintigraphy remained abnormal. None of the above patients had the most common form of I-MIBG false positivity, that is, uptake in the abdomen after retroperitoneal tumors are resected and renal function is impaired, leading to delayed or altered excretion of the radiotracer. Uncertainty in these situations is rare with tomographic (SPECT) imaging techniques or fusion MIBG/computed tomography (CT) that correlate uptake to anatomy; hybrid [F]fluorodeoxyglucose-positron emission tomography/CT can also be helpful in clarifying disease status. Relapse of high-risk neuroblastoma (NB) has long been viewed as a systemic event and tantamount to eventual death from disease or toxicity of retrieval therapy. Developments in the past decade, however, raise the welcome possibility that the absolute equivalence between relapse in these patients and a lethal outcome may no longer hold true. Thus, close monitoring using sensitive techniques may now be detecting focal or well-localized relapses. These might be controlled by surgery and/or radiotherapy, supplemented by relatively nontoxic systemic therapies that are noncrossresistant with prior treatments. For patients with no evidence of disease after treatment of highrisk NB, we continue to advocate close monitoring for recurrence. Despite being the most common study to reveal unsuspected relapse, I-MIBG scan was falsely negative in 16% of cases. Clearly, this scintigraphic evaluation cannot serve as a “stand-alone surveillance test” but should be part of a battery of tests required for accurately assessing relapse-free survival.
Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation
Authors: Charles G. Mullighan, Sue Heatley, Kathleen Doherty, Ferenc Szabo, Andrew Grigg, Timothy P. Hughes, Anthony P. Schwarer, Jeff Szer, Brian D. Tait, L. Bik To, Peter G. Bardy
Journal: Blood (2002)
Warfarin in the treatment of chronic urticaria/angio-oedema
Authors: R.J. Barlow, M.W. Greaves
Journal: British Journal of Dermatology (1992)

Journal Article Warfarin in the treatment of chronic urticaria/angio‐oedema Get access R.J. Barlow, R.J. Barlow St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.W. Greaves M.W. Greaves St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 126, Issue 4, 1 April 1992, Pages 415–416, https://doi.org/10.1111/j.1365-2133.1992.tb00694.x Published: 01 April 1992
The Comet-tail Artifact
Authors: DANIEL LICHTENSTEIN, GILBERT MÉZIÈRE, PHILIPPE BIDERMAN, AGNÈS GEPNER, OLIVIER BARRÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Can ultrasound be of any help in the diagnosis of alveolar-interstitial syndrome? In a prospective study, we examined 250 consecutive patients in a medical intensive care unit: 121 patients with radiologic alveolar-interstitial syndrome (disseminated to the whole lung, n = 92; localized, n = 29) and 129 patients without radiologic evidence of alveolar-interstitial syndrome. The antero-lateral chest wall was examined using ultrasound. The ultrasonic feature of multiple comet-tail artifacts fanning out from the lung surface was investigated. This pattern was present all over the lung surface in 86 of 92 patients with diffuse alveolar-interstitial syndrome (sensitivity of 93.4%). It was absent or confined to the last lateral intercostal space in 120 of 129 patients with normal chest X-ray (specificity of 93.0%). Tomodensitometric correlations showed that the thickened sub-pleural interlobular septa, as well as ground-glass areas, two lesions present in acute pulmonary edema, were associated with the presence of the comet-tail artifact. In conclusion, presence of the comet-tail artifact allowed diagnosis of alveolar-interstitial syndrome.
Covalent binding of reactive estrogen metabolites to microtubular protein as a possible mechanism of aneuploidy induction and neoplastic cell transformation.
Authors: B Epe, U Harttig, H Stopper, M Metzler
Journal: Environmental Health Perspectives (1990)

Neoplastic cell transformation induced by estrogens and some other carcinogens such as benzene appears to involve the induction of mitotic aneuploidy rather than DNA damage and point mutations. As metabolic activation may also play an important role in the mechanism of carcinogenesis of these nongenotoxic compounds, we have studied the interaction of reactive quinone metabolites of various estrogens and of benzene with the major microtubular protein, tubulin, in a cell-free system. Covalent binding of the radioactively labeled metabolites to the alpha- and beta-subunit of tubulin was found to depend on the structure of the metabolite. When the adducted tubulins were tested in vitro for their ability to polymerize to microtubules, inhibition of microtubule assembly was observed in every case, although to varying extents. It is proposed that the formation of covalent tubulin adducts may impair the formation of mitotic spindles and thus contribute to chromosomal nondisjunction and aneuploidy induction.
Real-Time, Aptamer-Based Tracking of Circulating Therapeutic Agents in Living Animals
Authors: Brian Scott Ferguson, David A. Hoggarth, Dan Maliniak, Kyle Ploense, Ryan J. White, Nick Woodward, Kuangwen Hsieh, Andrew J. Bonham, Michael Eisenstein, Tod E. Kippin, Kevin W. Plaxco, Hyongsok Tom Soh
Journal: Science Translational Medicine (2013)

An aptamer-based biosensor continuously measures the concentration of drug molecules in the blood of living animals and in patient samples.
Genetically Defined Subsets of Human Pancreatic Cancer Show Unique <i>In Vitro</i> Chemosensitivity
Authors: Yunfeng Cui, Jacqueline A. Brosnan, Amanda L. Blackford, Surojit Sur, Ralph H. Hruban, Kenneth W. Kinzler, Bert Vogelstein, Anirban Maitra, Luis A. Diaz, Christine A. Iacobuzio-Donahue, James R. Eshleman
Journal: Clinical Cancer Research (2012)

Pancreatic cancer is the fourth cause of death from cancer in the western world. Majority of patients present with advanced unresectable disease responding poorly to most chemotherapeutic agents. Chemotherapy for pancreatic cancer might be improved by adjusting it to individual genetic profiles. We attempt to identify genetic predictors of chemosensitivity to broad classes of anticancer drugs.Using a panel of genetically defined human pancreatic cancer cell lines, we tested gemcitabine (antimetabolite), docetaxel (antimicrotubule), mitomycin C (MMC; alkylating), irinotecan (topoisomerase I inhibitor), cisplatin (crosslinking), KU0058948 (Parp1 inhibitor), triptolide (terpenoid drug), and artemisinin (control).All pancreatic cancer cell lines were sensitive to triptolide and docetaxel. Most pancreatic cancer cells were also sensitive to gemcitabine and MMC. The vast majority of pancreatic cancer cell lines were insensitive to cisplatin, irinotecan, and a Parp1 inhibitor. However, individual cell lines were often sensitive to these compounds in unique ways. We found that DPC4/SMAD4 inactivation sensitized pancreatic cancer cells to cisplatin and irinotecan by 2- to 4-fold, but they were modestly less sensitive to gemcitabine. Pancreatic cancer cells were all sensitive to triptolide and 18% were sensitive to the Parp1 inhibitor. P16/CDKN2A-inactivated pancreatic cancer cells were 3- to 4-fold less sensitive to gemcitabine and MMC.Chemosensitivity of pancreatic cancer cells correlated with some specific genetic profiles. These results support the hypothesis that genetic subsets of pancreatic cancer exist, and these genetic backgrounds may permit one to personalize the chemotherapy of pancreatic cancer in the future. Further work will need to confirm these responses and determine their magnitude in vivo.
Antigen-specific immunosuppression in visceral leishmaniasis is cell mediated.
Authors: E M Carvalho, O Bacellar, A Barral, R Badaro, W D Johnson
Journal: Journal of Clinical Investigation (1989)

Visceral leishmaniasis is associated with an antigen-specific immunosuppression during the acute disease. Patients become responsive to Leishmania antigen in both in vivo and in vitro assays after successful antimony therapy. The cell type involved in the suppression of lymphocyte reactivity to Leishmania antigen was studied by selective depletion of mononuclear cell (MNC) populations and in co-cultivation experiments. Adherent cells were depleted on plastic and by passage on nylon wool columns. High-avidity Fc+ cells were depleted by adherence to BSA-anti-BSA complexes and OKT4+ and OKT8+ cells were depleted by treatment with monoclonal antibody (anti-OKT4+ and OKT8+) and complement. Depletion of MNC preparations of adherent cells, high-avidity Fc+ cells, OKT4+ cells and OKT8+ cells failed to restore the lymphocyte reactivity to Leishmania antigen. Antimony therapy was associated with restoration of the proliferative responses of unseparated MNC (before treatment 460 +/- 76 cpm and after treatment 4,293 +/- 1,442 cpm). Co-culture of frozen cells obtained before chemotherapy with autologous MNC obtained after treatment reduced the response of posttreatment cells to Leishmania antigen by 80%. We conclude that the antigenic specific suppression of lymphocyte proliferation in visceral leishmaniasis is cell mediated.
IHG-1 Amplifies TGF-β1 Signaling and Is Increased in Renal Fibrosis
Authors: Madeline Murphy, Neil G. Docherty, Brenda Griffin, Jillian Howlin, Emmett McArdle, Ruth McMahon, Holger Schmid, Matthias Kretzler, Alejandra Droguett, Sergio Mezzano, Hugh R. Brady, Fiona Furlong, Catherine Godson, Finian Martin
Journal: Journal of the American Society of Nephrology (2008)

Induced in high glucose-1 (IHG-1) is an evolutionarily conserved gene transcript upregulated by high extracellular glucose concentrations, but its function is unknown. Here, it is reported that the abundance of IHG-1 mRNA is nearly 10-fold higher in microdissected, tubule-rich renal biopsies from patients with diabetic nephropathy compared with control subjects. In the diabetic nephropathy specimens, in situ hybridization localized IHG-1 to tubular epithelial cells along with TGF-beta1 and activated Smad3, suggesting a possible role in the development of tubulointerstitial fibrosis. Supporting this possibility, IHG-1 mRNA and protein expression also increased with unilateral ureteral obstruction. In the HK-2 proximal tubule cell line, overexpression of IHG-1 increased TGF-beta1-stimulated expression of connective tissue growth factor and fibronectin. IHG-1 was found to amplify TGF-beta1-mediated transcriptional activity by increasing and prolonging phosphorylation of Smad3. Conversely, inhibition of endogenous IHG-1 with small interference RNA suppressed transcriptional responses to TGF-beta1. In summary, IHG-1, which increases in diabetic nephropathy, may enhance the actions of TGF-beta1 and contribute to the development of tubulointerstitial fibrosis.
Nitric Oxide Induces Resensitization of P2Y Nucleotide Receptors in Cultured Rat Mesangial Cells
Authors: Ruisheng Liu, Antonio M. Gutie[Combining Acute Accent]rrez, Avi Ring, A. Erik G. Persson
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Receptor desensitization of G protein–coupled receptors (GPCRs), which occurs during short-term (seconds to minutes) exposure of cells to agonists, is mediated by phosphorylation and receptor endocytosis. Recycling of the receptors is a requisite for resensitization of the response. The mechanisms that attenuate signaling by GPCRs are of considerable importance to regulation of intercellular signaling and maintenance of their ability to respond to agonists over time. This study evaluates the effect of nitric oxide (NO) on P2Y nucleotide receptor resensitization in cultured rat glomerular mesangial cells. The NO production in cultured mesangial cells was measured by using confocal microscopy and the fluorescence NO indicator 4,5-diaminofluorescein diacetate (DAF-2 DA). L-arginine increased and Nω-nitro-L-arginine methyl ester (L-NAME) decreased NO production significantly (P < 0.05). Calcium responses to ATP were measured with fura-2 and imaging techniques. Repeated stimulation with ATP results in receptor desensitization that is characterized by lower calcium peak amplitude. Desensitization was induced by challenging mesangial cells with four consecutive 2-min pulses of ATP (0.1 mM) separated by 4.5-min control perfusions. Intracellular calcium concentration ([Ca2+]i) increase evoked by second, third, and fourth ATP challenges were about 40%, 26%, and 18% of the first one. The NO precursor, L-arginine (10 mM), and the NO donors, spermine-NONOate (500 μM) and sodium nitroprusside (SNP) (1 mM), were added before and during a fourth ATP challenge. Spermine-NONOate and L-arginine induced a recovery of the [Ca2+]i response to the fourth ATP challenge (P < 0.01 and 0.05, respectively). The NO synthase inhibitor, L-NAME (5 mM), applied along with ATP, was shown to enhance desensitization. 1H-(1,2,4)oxadiazolo(4,3-α)quinoxalin-1-one (ODQ, 30 μM), an inhibitor of guanylate cyclase, was used along with L-arginine, SNP, or spermine-NONOate. There was no significant difference with or without ODQ. Neither ODQ nor 8-Br-cGMP, an analog of cGMP, at different concentrations showed effects on ATP-stimulated [Ca2+]i. There was no elevation of [Ca2+]i when the cells were challenged by different concentrations (1 μM, 100 μM, 1 mM, 20 mM, and 30 mM) of caffeine, caffeine plus ATP (0.1 mM), and 4-chloro-3-ethylphenol (100 μM, 500 μM, and 1 mM), a new agonist of ryanodine receptors. The results indicate that NO can increase the P2Y receptor resensitization in rat glomerular mesangial cells by acting through a cGMP-independent pathway. No evidence was found for the existence of ryanodine-sensitive intracellular calcium stores in rat mesangial cells.
Eosinophil-active cytokine from mononuclear cells cultured with L-tryptophan products: An unexpected consequence of endotoxin contamination
Authors: Hirohito Kita, Arthur N. Mayeno, Cornelia M. Weyand, Jörg J. Goronzy, Deborah A. Weiler, Steven K. Lundy, John S. Abrams, Gerald J. Gleich
Journal: Journal of Allergy and Clinical Immunology (1995)
American Society of Clinical Oncology Identifies Five Key Opportunities to Improve Care and Reduce Costs: The Top Five List for Oncology
Authors: Lowell E. Schnipper, Thomas J. Smith, Derek Raghavan, Douglas W. Blayney, Patricia A. Ganz, Therese Marie Mulvey, Dana S. Wollins
Journal: Journal of Clinical Oncology (2012)

Lowell E. Schnipper, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Thomas J. Smith, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD; Derek Raghavan, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC; Douglas W. Blayney, Stanford Cancer Institute, Stanford University School of Medicine, Stanford; Patricia A. Ganz, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA; Therese Marie Mulvey, Southcoast Center for Cancer Care, Southcoast Health System, New Bedford, MA; Dana S. Wollins, American Society of Clinical Oncology, Alexandria, VA.