tbuckley/cabot-search huggingface dataset:
An interleukin-17–mediated paracrine network promotes tumor resistance to anti-angiogenic therapy
Authors: Alicia S Chung, Xiumin Wu, Guanglei Zhuang, Hai Ngu, Ian Kasman, Jianhuan Zhang, Jean-Michel Vernes, Zhaoshi Jiang, Y Gloria Meng, Franklin V Peale, Wenjun Ouyang, Napoleone Ferrara
Journal: Nature Medicine (2013)
Uncommon Presentations of Malignancies
Authors: Vinay Raja, David Bessman
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.106 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12885823 Uncommon Presentations of Malignancies CASE 4. TUMOR IMPLANTATION AFTER PNEUMONECTOMY FOR LUNG CANCER Vinay RajaxVinay RajaSearch for articles by this author , David BessmanxDavid BessmanSearch for articles by this author Show More Departments of Medical Oncology and Internal Medicine, University of Texas Medical Branch Galveston, TX https://doi.org/10.1200/JCO.2003.07.106 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice
Authors: Jonathan A. Hill, David A. Bell, William Brintnell, David Yue, Bret Wehrli, Anthony M. Jevnikar, David M. Lee, Wolfgang Hueber, William H. Robinson, Ewa Cairns
Journal: The Journal of Experimental Medicine (2008)

Rheumatoid arthritis (RA) is a common autoimmune disease that afflicts the synovium of diarthrodial joints. The pathogenic mechanisms inciting this disease are not fully characterized, but may involve the loss of tolerance to posttranslationally modified (citrullinated) antigens. We have demonstrated that this modification leads to a selective increase in antigenic peptide affinity for major histocompatibility complex (MHC) class II molecules that carry the RA-associated shared epitope, such as HLA-DRB1*0401 (DR4). We describe the induction of arthritis in DR4-IE transgenic (tg) mice with citrullinated fibrinogen, a protein commonly found in inflamed synovial tissue and a frequent target of autoantibodies in RA patients. The disease induced in these mice was characterized by synovial hyperplasia followed by ankylosis, but lacked a conspicuous polymorphonuclear cell infiltrate. Immunological analysis of these mice through T cell epitope scanning and antibody microarray analysis identified a unique profile of citrulline-specific reactivity that was not found in DR4-IE tg mice immunized with unmodified fibrinogen or in wild-type C57BL/6 mice immunized with citrullinated fibrinogen, two conditions where arthritis was not observed. These observations directly implicate citrullinated fibrinogen as arthritogenic in the context of RA-associated MHC class II molecules.
Diabetes Translation Research: Where Are We and Where Do We Want To Be?
Authors: K. M. Venkat Narayan, Evan Benjamin, Edward W. Gregg, Susan L. Norris, Michael M. Engelgau
Journal: Annals of Internal Medicine (2004)

Translation research transforms currently available knowledge into useful measures for everyday clinical and public health practice. We review the progress in diabetes translation research and identify future challenges and opportunities in this field. Several promising interventions to optimize implementation of efficacious diabetes treatments are available. Many of these interventions, singly or in combination, need to be more formally tested in larger randomized or quasi-experimental practical trials using outcomes of special interest to patients (for example, patient satisfaction and quality of life) and policymakers (for example, cost and cost-effectiveness). The long-term outcomes (such as morbidity, mortality, quality of life, and costs) of strategies aimed at improving diabetes care must be assessed. Translation research also needs to incorporate ways of studying complex systems of care. The challenges and opportunities offered by translation research are tremendous.
Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Incorporating a “Superior” Slow Pathway
Authors: Yoshiaki Kaneko, Shigeto Naito, Kaoru Okishige, Itsuro Morishima, Takeshi Tobiume, Tadashi Nakajima, Tadanobu Irie, Masaki Ota, Takafumi Iijima, Takashi Iizuka, Mio Tamura, Shuntaro Tamura, Akihiro Saito, Osamu Igawa, Ritsushi Kato, Kazuo Matsumoto, Fumio Suzuki, Masahiko Kurabayashi
Journal: Circulation (2015)

The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed.We studied 6 women and 2 men (age, 74 ± 7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378 ± 119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each.sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation.
Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors
Authors: M. M. Singh, C. A. Manton, K. P. Bhat, W.-W. Tsai, K. Aldape, M. C. Barton, J. Chandra
Journal: Neuro-Oncology (2011)

Glioblastoma multiforme (GBM) is a particularly aggressive brain tumor and remains a clinically devastating disease. Despite innovative therapies for the treatment of GBM, there has been no significant increase in patient survival over the past decade. Enzymes that control epigenetic alterations are of considerable interest as targets for cancer therapy because of their critical roles in cellular processes that lead to oncogenesis. Several inhibitors of histone deacetylases (HDACs) have been developed and tested in GBM with moderate success. We found that treatment of GBM cells with HDAC inhibitors caused the accumulation of histone methylation, a modification removed by the lysine specific demethylase 1 (LSD1). This led us to examine the effects of simultaneously inhibiting HDACs and LSD1 as a potential combination therapy. We evaluated induction of apoptosis in GBM cell lines after combined inhibition of LSD1 and HDACs. LSD1 was inhibited by targeted short hairpin RNA or pharmacological means and inhibition of HDACs was achieved by treatment with either vorinostat or PCI-24781. Caspase-dependent apoptosis was significantly increased (>2-fold) in LSD1-knockdown GBM cells treated with HDAC inhibitors. Moreover, pharmacologically inhibiting LSD1 with the monoamine oxidase inhibitor tranylcypromine, in combination with HDAC inhibitors, led to synergistic apoptotic cell death in GBM cells; this did not occur in normal human astrocytes. Taken together, these results indicate that LSD1 and HDACs cooperate to regulate key pathways of cell death in GBM cell lines but not in normal counterparts, and they validate the combined use of LSD1 and HDAC inhibitors as a therapeutic approach for GBM.
Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes.
Authors: M Kobayashi, L Fitz, M Ryan, R M Hewick, S C Clark, S Chan, R Loudon, F Sherman, B Perussia, G Trinchieri
Journal: The Journal of Experimental Medicine (1989)

We have identified and purified a novel cytokine, NK cell stimulatory factor (NKSF), from the cell-free supernatant fluid of the phorbol diester-induced EBV-transformed human B lymphoblastoid cell line RPMI 8866. NKSF activity is mostly associated to a 70-kD anionic glycoprotein. The purified 70-kD protein, isolated from an SDS-PAGE gel, yields upon reduction two small species of molecular masses of 40 and 35 kD, suggesting that this cytokine is a heterodimer. When added to human PBL, purified NKSF preparations induce IFN-gamma production and synergize with rIL-2 in this activity, augment the NK cell-mediated cytotoxicity of PBL preparations against both NK-sensitive and NK-resistant target cell lines, and enhance the mitogenic response of T cells to mitogenic lectins and phorbol diesters. The three activities remain associated through different purification steps resulting in a 9,200-fold purification, and purified NKSF mediates the three biological activities at concentrations in the range of 0.1-10 pM. These data strongly suggest that the same molecule mediates these three activities, although the presence of traces of contaminant peptides even in the most purified NKSF preparations does not allow us to exclude the possibility that distinct biologically active molecules have been co-purified. The absence of other known cytokines in the purified NKSF preparations, the unusual molecular conformation of NKSF, the high specific activity of the purified protein, and the spectrum of biological activities distinguish NKSF from other previously described cytokines.
Spinal cord stimulation (SCS) to restore cough in spinal cord injury (SCI) subjects: Long-term follow-up
Authors: Anthony DiMarco, Dana Hromyak, Krzysztof Kowalski
Journal: European Respiratory Journal (2014)

Background: SCS has been shown to restore an effective cough mechanism in SCI subjects.

Objective: To re-assess the clinical parameters related to use of the cough system in subjects who have had the implant for a minimum of 2 years (mean 4.6±0.6 years), well beyond the period of close follow-up.

Outcome Measures: Maximum airway pressure generation (P) and other clinical assessments related to secretion management.

Results: Each subject continued to use the device on a regular, usually daily, basis. Pre-implant P was 28±5cmH2O. During SCS, P were 103±20 and 108±23cmH2O at the 1 year and mean 4.60 year follow-up points, respectively (p<0.05 compared to pre-implant and NS when compared to 1 year follow-up during SCS).There were significant improvements in each of the measures related to airway clearance, and the need for alternative methods of secretion removal was virtually eliminated in each subject. The need for trained caregivers to provide other means of secretion management and the incidence of respiratory tract infections remained significantly below the pre-implant values (p<0.05). All subjects reported reduce anxiety and embarrassment related to secretion clearance, greater mobility and consequent improvement in social interaction and improvement in overall life quality.

Conclusion: Subjects continued to use the system on a long-term basis beyond the period of close follow-up and to continued derive significant clinical benefits.

Support: NIH: NIH-NINDS (R01NS049516 and RC1NS068576), NCRR (M01RR0080 and UL1RR024989).

Disclosure: Dr. DiMarco is a Founder of and has a significant financial interest in Synapse BioMedical, Inc, a manufacturer of diaphragm pacing systems.
Apoptosis Repressor with Caspase Recruitment Domain Contributes to Chemotherapy Resistance by Abolishing Mitochondrial Fission Mediated by Dynamin-Related Protein-1
Authors: Jian-Xun Wang, Qian Li, Pei-Feng Li
Journal: Cancer Research (2009)

Abstract One obstacle of cancer therapy is the development of cancer resistance to chemotherapy. The molecular mechanisms by which the resistance is developed remain to be fully understood. Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous antiapoptotic protein. Here, we report that ARC contributes to chemotherapy resistance by abolishing mitochondrial fission mediated by dynamin-related protein-1 (Drp1). Our results show that both HeLa and human gastric cancer (SGC-7901) cells have a high expression level of ARC. Doxorubicin at a low dose can slightly induce apoptosis in HeLa and SGC-7901 cells. In contrast, knockdown of ARC by its RNA interference enables the same low dose of doxorubicin to significantly induce apoptosis in HeLa and SGC-7901 cells. These data indicate that ARC is responsible for the cell resistance to doxorubicin treatment. Mitochondrial fission has recently been shown to be involved in triggering apoptosis. In exploring the molecular mechanism by which ARC participates in antagonizing doxorubicin-induced apoptosis, we observed that doxorubicin is able to induce mitochondrial fission that can be inhibited by ARC. Our results further show that Drp1 accumulates in mitochondria and mediates the signal of doxorubicin to induce mitochondrial fission. ARC is able to prevent Drp1 accumulations in mitochondria. Finally, we identified that PUMA is required for Drp1 accumulations in mitochondria. ARC inhibits Drp1 accumulations in mitochondria by directly binding to PUMA. Taken together, our results reveal a chemotherapy-resistant model in which ARC inhibits PUMA-mediated Drp1 accumulations in mitochondria and the consequent mitochondrial fission. [Cancer Res 2009;69(2):492–500]
Apolipoprotein B, fibrinogen, HDL cholesterol, and apolipoprotein(a) phenotypes predict coronary artery disease in hemodialysis patients.
Authors: M Koch, B Kutkuhn, E Trenkwalder, D Bach, B Grabensee, H Dieplinger, F Kronenberg
Journal: Journal of the American Society of Nephrology (1997)

Patients with end-stage renal disease have a markedly elevated risk for coronary artery disease (CAD). Lipids and most lipoproteins, however, seem to be not predictive for CAD in these patients. Although there is clear evidence that lipoprotein(a) [Lp(a)] is significantly elevated in these patients, no study with a sufficiently large group of hemodialysis patients has investigated the relationship between CAD and Lp(a), as well as the genetically determined apolipoprotein(a) [apo(a)] phenotype. This cross-sectional study determines the prevalence of CAD in relation to the cardiovascular risk profile in an unselected population of 607 hemodialysis patients, of which 33% were diabetic patients. Twenty-six percent (n = 158) of all patients suffered from CAD as diagnosed by a definitive myocardial infarction (n = 102) and/or at least one stenosis >50% of a coronary artery (n = 143). In univariate analysis, several classic risk factors, including the concentration of lipids, lipoproteins, apolipoproteins, and fibrinogen, correlated with CAD. Lp(a) in patients with CAD showed only a tendency to higher levels, without reaching significance, compared with patients without CAD (26.6 +/- 30.8 mg/dl versus 22.1 +/- 30.4 mg/dl, P = 0.10). The frequency of low molecular weight apo(a) isoforms, however, was significantly greater in the group with CAD (34.8% versus 23.6%, P < 0.01). Stepwise logistic regression analysis found seven variables associated with CAD: apolipoprotein B, the low molecular weight apo(a) phenotype, male sex, age, fibrinogen, diabetes mellitus, and HDL cholesterol. The association of these variables with CAD differed depending on age. These results indicate that, besides classic risk factors such as age, sex, and diabetes mellitus, additional factors of the lipoprotein and fibrinolytic system contribute to the high prevalence of CAD in hemodialysis patients.
A SOLUBLE ANTIGEN OF LYMPHOCYTIC CHORIOMENINGITIS
Authors: J. E. Smadel, M. J. Wall
Journal: The Journal of Experimental Medicine (1940)

Anti-soluble substance antibodies and neutralizing substances, which develop following infection with the virus of lymphocytic choriomeningitis, appear to be separate entities. The times of appearance and regression of the two antibodies are different in both man and the guinea pig; the antisoluble substance antibodies appear earlier and remain a shorter time. Moreover, mice develop them but no demonstrable neutralizing substances. Injection of formalin-treated, virus-free extracts containing considerable amounts of soluble antigen fails to elicit anti-soluble substance antibodies and to induce immunity in normal guinea pigs; administration of such preparations to immune pigs, however, is followed by a marked increase in the titer of anti-soluble substance antibodies in their serum. On the other hand, suspensions of formolized washed virus are effective in normal guinea pigs in stimulating both anti-soluble substance antibodies and protective substances, and in inducing immunity to infection.
Modular drug transporters with diphtheria toxin translocation domain form edged holes in lipid membranes
Authors: Yuri V. Khramtsov, Tatyana I. Rokitskaya, Andrey A. Rosenkranz, Georgiy A. Trusov, Nikolay V. Gnuchev, Yuri N. Antonenko, Alexander S. Sobolev
Journal: Journal of Controlled Release (2008)
Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-β and STAT3 activation
Authors: Atsushi Hosui, Akiko Kimura, Daisuke Yamaji, Bing-mei Zhu, Risu Na, Lothar Hennighausen
Journal: The Journal of Experimental Medicine (2009)

The molecular mechanisms underlying the development of hepatocellular carcinoma are not fully understood. Liver-specific signal transducer and activator of transcription (STAT) 5A/B–null mice (STAT5-LKO) were treated with carbon tetrachloride (CCl4), and histological analyses revealed liver fibrosis and tumors. Transforming growth factor (TGF)–β levels and STAT3 activity were elevated in liver tissue from STAT5-LKO mice upon CCl4 treatment. To define the molecular link between STAT5 silencing and TGF-β up-regulation, as well as STAT3 activation, we examined STAT5-null mouse embryonic fibroblasts and primary hepatocytes. These cells displayed elevated TGF-β protein levels, whereas messenger RNA levels remained almost unchanged. Protease inhibitor studies revealed that STAT5 deficiency enhanced the stability of mature TGF-β. Immunoprecipitation and immunohistochemistry analyses demonstrated that STAT5, through its N-terminal sequences, could bind to TGF-β and that retroviral-mediated overexpression of STAT5 decreased TGF-β levels. To confirm the in vivo significance of the N-terminal domain of STAT5, we treated mice that expressed STAT5 lacking the N terminus (STAT5-ΔN) with CCl4. STAT5-ΔN mice developed CCl4-induced liver fibrosis but no tumors. In conclusion, loss of STAT5 results in elevated TGF-β levels and enhanced growth hormone–induced STAT3 activity. We propose that a deregulated STAT5–TGF-β–STAT3 network contributes to the development of chronic liver disease.
Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
Authors: Thomas B. Campbell, Laura M. Smeaton, N. Kumarasamy, Timothy Flanigan, Karin L. Klingman, Cynthia Firnhaber, Beatriz Grinsztejn, Mina C. Hosseinipour, Johnstone Kumwenda, Umesh Lalloo, Cynthia Riviere, Jorge Sanchez, Marineide Melo, Khuanchai Supparatpinyo, Srikanth Tripathy, Ana I. Martinez, Apsara Nair, Ann Walawander, Laura Moran, Yun Chen, Wendy Snowden, James F. Rooney, Jonathan Uy, Robert T. Schooley, Victor De Gruttola, James Gita Hakim
Journal: PLoS Medicine (2012)

Background Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen. Trial Registration www.ClinicalTrials.gov NCT00084136 Please see later in the article for the Editors' Summary.
Medical clowns ease anxiety and pain perceived by children undergoing allergy prick skin tests
Authors: A. Goldberg, T. Stauber, O. Peleg, P. Hanuka, L. Eshayek, R. Confino‐Cohen
Journal: Allergy (2014)

Intervention of medical clowns (MC) during various medical procedures performed in children has been used to relieve anxiety and pain. Their role in allergy skin testing has never been evaluated.To evaluate whether MC can diminish pain and anxiety perceived by children undergoing allergy skin prick tests (SPT).In a prospective, randomized, controlled, and blinded study, children undergoing SPT were or were not accompanied by MC. All parents and children ≥8 years completed the State-Trait Anxiety Inventory (STAI) before and after SPT. Videotapes recorded during the procedure were scored for anxiety (m-YPAS) for all children and for pain (FLACC) for children 2-7 years old by a psychologist who was unaware of the MC's presence. After SPT, children ≥8 years completed a visual analog score (VAS) for pain.Ninety-one children (mean age 8.2 years, M/F = 54/37) were recruited of whom 45 were accompanied by clowns. A significant reduction in state-STAI was found in the clowns group, in both parents and children, when compared with the regular group (26.9 ± 6.6 and 32.3 ± 10.0; P = 0.004, and 27.1 ± 4.2 and 34.3 ± 7.6; P = 0.002, respectively). Both m-YPAS and FLACC were reduced in the clowns group compared with the regular one. In the clowns group, m-YPAS positively correlated with both VAS and FLACC (P = 0.000 and 0.002, respectively). m-YPAS was positively correlated with FLACC in the regular group (P = 0.000).Medical clowns significantly decrease the level of anxiety perceived by both children undergoing allergy SPT and their parents, as well as the pain perceived by young children.
Direct expenditures for the treatment of allergic rhinoconjunctivitis in 1996, including the contributions of related airway illnesses
Authors: Nancy F. Ray, James N. Baraniuk, Mae Thamer, Cheryl S. Rinehart, Peter J. Gergen, Michael Kaliner, Shelby Josephs, Yung-Hao Pung
Journal: Journal of Allergy and Clinical Immunology (1999)