tbuckley/cabot-search huggingface dataset:
Targeting immune evasion in cancer immunotherapy.
Authors: Eli Gilboa, Smita Nair, David Boczkowski, Jaewoo Lee, Martin Fassnacht
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

SY04-02 

Vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) augments tumor immunity in murine models through improved tumor antigen presentation by mature CD11b+ dendritic cells and macrophages. CD4+ and CD8+ T cells, CD1d-restricted invariant NKT cells, and antibodies mediate protective immunity. We have performed several Phase I clinical trials of this immunization strategy, using adenoviral mediated gene transfer to engineer autologous tumor cells to secrete human GM-CSF, in patients with advanced melanoma, non-small lung carcinoma, ovarian carcinoma, and myeloid leukemia. These investigations have demon strated that vaccination increases tumor immunity in the majority of subjects, as distant metastases become densely infiltrated with T and B cells that accomplish extensive tumor necrosis. Antibody based-expression cloning technologies have revealed a large number of novel targets of these vaccine-induced responses, with evidence of a coordinated antigen-specific cellular and humoral reaction. Despite improved immunity, however, the majority of vaccinated patients eventually succumb to progressive disease. While the evolution of antigen-loss variants presents one obstacle to durable tumor control, negative immune regulation constitutes an additional major challenge. In preliminary clinical studies, the administration of a fully human monoclonal antibody that blocks cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) to previously vaccinated patients evokes additional tumor destruction with lymphocyte and granulocyte infiltrates and the disruption of the tumor vasculature. CTLA-4 blockade may also breach tolerance to normal tissues, as indicated by the development of autoimmunity. A key issue of ongoing investigation is to determine whether tumor destruction and serious autoimmunity can be dissociated. Studies of patients responding to CTLA-4 blockade have begun to clarify the ways in which protective immunity can be safely induced and, in so doing, immunosuppressive mechanisms reversed.
Therapeutic induction of tolerance by IL-10-differentiated dendritic cells in a mouse model of house dust mite-asthma*
Authors: M. Lu, W. Dawicki, X. Zhang, H. Huang, A. Nayyar, J. R. Gordon
Journal: Allergy (2011)

To cite this article: Lu M, Dawicki W, Zhang X, Huang H, Nayyar A, Gordon JR. Therapeutic induction of tolerance by IL-10-differentiated dendritic cells in a mouse model of house dust mite-asthma. Allergy 2011; 66: 612–620. Abstract Background: It has been reported that retrovirally transduced IL-10-expressing dendritic cells can reverse the asthma phenotype in mice, but that i.v. delivery of dendritic cells differentiated with IL-10 alone (DC10) does not. We report herein DC10 can be highly effective therapeutically in experimental asthma. Methods: BALB/c mice were sensitized by airway exposure to house dust mite (HDM) without use of adjuvants, then treated with 106 allergen-presenting DC10. We assessed the airway hyperresponsiveness (AHR) to methacholine, circulating levels of IgE and IgG1, and airway recall responses to HDM allergen, including eosinophilia and Th2 cytokines. We also asked whether the DC10 treatments induced tolerance through activation of pulmonary regulatory T cell activities. Results: In vitro, cognate-, but not irrelevant-, allergen-presenting DC10 productively engaged pulmonary Th2-phenotype CD4+ cells magnetically sorted from HDM-asthmatic mice in Forster (or fluorescence) resonance energy transfer assays. In vivo, treatment of HDM-asthmatic mice with HDM, but not ovalbumin-presenting DC10 abrogated AHR within 4 weeks, and significantly reduced airway eosinophilia, IL-4, IL-5, and IL-13 responses, and circulating HDM-specific IgE and IgG1 levels (each, P ≤ 0.01 versus control mice). CD4+CD25+Foxp3+ cells from the lungs of the DC10-treated mice, but not those from asthmatic animals, up-regulated expression of the activated regulatory T cell markers CTLA4 and LAG3, and passive transfer of pulmonary CD4+ T cells from these mice induced allergen tolerance in HDM-asthmatic recipients. Conclusions: These findings indicate that allergen-presenting DC10 treatments up-regulate T cell regulatory activities and thereby induce allergen-specific tolerance in a relevant model of human asthma.
814. Integration Sites Used by the PhiC31 Site-Specific Integrase in the Human Genome
Authors: Thomas W. Chalberg, Daniel S. Ginsburg, Patrick J. Kirby, Eric C. Olivares, Joylette L. Portlock, Bhaskar Thyagarajan, Michele P. Calos
Journal: Molecular Therapy (2004)

Our goal is to perform non-viral gene therapy by using efficient site-specific plasmid integration into the human genome. This approach offers a dual safety advantage: viral complexity, toxicity, and immunogenicity are avoided, and site-specific integration reduces the risk of insertional mutagenesis. We have developed site-specific integration systems by using unidirectional phage integrases from the serine recombinase family. In nature, these phage integrases catalyze precise recombination between a 40 base pair attP recognition site encoded in the phage genome and a similarly-sized attB site in the bacterial chromosome. We have shown that some phage integrases can mediate integration of vectors bearing attB into mammalian chromosomes at genomic sequences that are similar to attP, termed pseudo attP sites. This integration is associated with strong long-term transgene expression in transfected cells and tissues that is suitable for gene therapy.
Innovations of the Americans With Disabilities Act
Authors: Mark A. Rothstein
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sudden Cardiac Death Among Women in the United States
Authors: Janice B. Schwartz
Journal: Circulation (2003)

The recent article by Albert and colleagues 1 is on a topic of much interest because, as noted by the authors, the rate of sudden cardiac death among middle-aged women is increasing.The authors investigated relationships between potential risk factors for cardiovascular disease and sudden death in the Nurses' Health Study.I cannot understand why the authors failed to comment on or even discuss the potential role of medications or pharmacologically active agents that the women with sudden death may have been consuming.3][4] Although it appears that medication information may not have been routinely collected during the Nurses' Health Study, the authors state that they reviewed medical records of all the women with sudden death, as well as reports from next of kin for the current investigation.Information on medication and nutraceutical use would be of great value in elucidating potential causes for sudden death in the women studied.
The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors
Authors: Roberto Pola, Leona E. Ling, Marcy Silver, Michael J. Corbley, Marianne Kearney, R. Blake Pepinsky, Renee Shapiro, Frederick R. Taylor, Darren P. Baker, Takayuki Asahara, Jeffrey M. Isner
Journal: Nature Medicine (2001)
Letter: 2 papers on BBB during tachycardia.
Authors: R Slama
Journal: Circulation (1975)

If the facilities to record the His bundle electrogram are not available we would recommend prophylactic pacing in every patient who develops bifascicular block in association with acute anteroseptal infarction provided that it appears within 24 hours after onset of infarction, that the bifascicular block persists for at least 6 hours and that signs of pulmonary edema or cardiogenic shock are absent at the time of appearance of the conduction disturbance.
Prognosis With Asymptomatic Pulmonary Nodules
Authors: M H Kollef
Journal: JAMA (1995)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 12015: Patients With Confirmed Statin Myalgia Do Not Exhibit Changes in Muscle Strength or Aerobic Performance
Authors: Amanda L Zaleski, Beth A Taylor, Lindsay Lorson, Charles M White, Paul D Thompson
Journal: Circulation (2014)

Background:  There are observational reports of decreased muscle strength and aerobic performance in patients with statin myalgia, but no rigorous assessments of strength and aerobic performance in patients with confirmed statin myalgia. We examined the effect of simvastatin (SIMVA) 20 mg daily (mg/d) on muscle strength and aerobic performance in patients with confirmed statin myalgia.   Methods:  Eighteen subjects (60 ± 10 years) whose statin myalgia was confirmed by their developing pain with SIMVA but not with placebo during an 8-week, double-blind crossover lead-in trial were randomized to SIMVA 20 mg/d for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), isometric handgrip strength, isometric and isokinetic arm and leg muscle strength, respiratory exchange ratio (RER) and maximal oxygen uptake (VO2max) were measured before and after SIMVA treatment.   Results:  BPI pain severity (from 0.0 ± 0.0 to 1.7 ± 2.4 points) and interference (from 0.0 ± 0.0 to 1.4 ± 2.5 points) scores increased (both p  0.10) for 13 measured variables), RER (from 0.86 ± 0.08 to 0.87 ± 0.06; p = 0.92) and VO2max (from 24.5 ± 5.0 to 23.9 ± 5.1 mL/kg/min; p = 0.19) did not change with SIMVA.   Conclusions:  Statin myalgia is not associated with decreases in muscle strength, resting fuel utilization, and aerobic performance.   Trial Registration: NCT01140308
Whole-Arm Ultrasound to Rule Out Suspected Upper-Extremity Deep Venous Thrombosis in Outpatients
Authors: Michelangelo Sartori, Ludovica Migliaccio, Elisabetta Favaretto, Carlotta Brusi, Eleonora Conti, Giuseppina Rodorigo, Benilde Cosmi
Journal: JAMA Internal Medicine (2015)

Whole-Arm Ultrasound to Rule Out Suspected Upper-Extremity Deep Venous Thrombosis in OutpatientsUpper-extremity deep venous thrombosis (UE-DVT) accounts for approximately 14% of all cases of DVT. 1 Because UE-DVT may provoke pulmonary embolism (PE), prompt diagnosis is necessary to select the patients who require anticoagulation.This study aimed to evaluate the failure rate of ultrasonographic screening for UE-DVT. Methods | Study Design.A prospective management study was conducted from January 1, 2011, through December 31, 2013, in the Angiology and Blood Coagulation Unit, University Hospital, Bologna, Italy, a tertiary care teaching hospital, in outpatients referred by general practice physicians to the vascular emergency department for suspected symptomatic DVT or superficial venous thrombosis (SVT) of the upper extremities.Exclusion criteria were age younger than 18 years, pregnancy or puerperium, PE symptoms, life expectancy of less than 3 months, and a need for anticoagulant therapy or anticoagulation lasting more than 48 hours.We enrolled eligible consecutive patients during business days.Patients with DVT or SVT received anticoagulants while patients with either negative or initially inconclusive findings from the ultrasonographic screening were not treated and were followed up for 3 months.The outcome was the cumulative 3-month incidence of objectively confirmed symptomatic PE and/or UE-DVT.All events were adjudicated by one of us (B.C.) who was not involved in patient enrollment or follow-up.Participants who were lost to follow-up were removed a priori from the analysis.
Ventricular and sulcal size at the onset of psychosis
Authors: William G. Iacono, Geoffrey N. Smith, Margaret Moreau, Morton Beiser, Jonathan A. E. Fleming, Tsung-yi Lin, Borys Flak
Journal: American Journal of Psychiatry (1988)

To determine whether abnormalities in brain morphology are present at the onset of illness, patients with schizophrenia, schizophreniform and bipolar disorders, and major depression who were experiencing their first episodes of psychosis were compared with normal and medical control subjects. The schizophrenic patients had larger third ventricles but not larger lateral ventricles or cortical sulci than the normal subjects. The other psychotic patients did not differ from the normal group on these measures. A different pattern of results emerged when the medical patients were used for comparison, indicating that the choice of control group can influence the findings of computerized tomography studies.
Rewriting the Script
Authors: Daniel Saal
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
888. A BMP2/7 Fusion Gene Enhances Osteoblastic Differentiation in Mesenchymal Cells
Authors: Wei Zhu, Oheneba Boachie-Adjei, Bernard Rawlins, Ronald G. Crystal, Chisa Hidaka
Journal: Molecular Therapy (2004)

While recombinant bone morphogenic proteins (rBMPs) are homodimers, several studies have suggested that heterodimeric BMPs resulting from the co-expression of two different BMP genes might be more potent. Previously, we have shown that co-transfection of target cells with adenovirus (Ad) vectors encoding BMP2 or BMP7 results in enhanced osteoblastic differentiation of mesenchymal cells in vitro and bone formation in vivo when compared to either vector alone. In the current study, we constructed a novel BMP2/7 fusion gene encoding both BMP2 and BMP7 fused by a linker, and show that transfection with this gene results in the expression of biologically active BMP2/7 heterodimer.
The importance of proline metabolism under conditions of nutrient stress
Authors: Jui Pandhare, Sandra Coopoer, Steven Donald, James Phang
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4501 

Under conditions of nutrient stress, cells switch to a survival mode catabolizing cellular and tissue constituents for energy. Proline metabolism is especially important in nutrient stress because it is readily available from the breakdown of extracellular matrix (ECM), and the degradation of proline by proline oxidase (POX), a mitochondrial inner membrane enzyme, can generate ATP. The cycling of proline and product pyrroline-5-carboxylate functions as a redox shuttle and the electrons from proline can be used for generation of ATP or ROS. Thus, the degradation of proline may bioenergetically maintain survival or mediate apoptosis. We found that accompanying the downregulation of mTOR by amino acid or glucose deprivation, POX expression and activity were upregulated. A 3-4 fold increase in POX catalytic activity was obtained with withdrawal of either glucose or amino acids. Rapamycin, the inhibitor of mTOR, markedly upregulated POX, supporting the role of mTOR in the POX response to nutrient stress. In spite of nutrient deprivation, ATP levels were maintained with increased proline degradation. Following rapamycin treatment an initial decline in intracellular ATP levels was obtained. However, by 12 h, the increase in POX activity was accompanied by a rise in ATP levels. This increase in ATP levels was suppressed when POX was inhibited indicating the contributions of POX and proline to the maintenance of ATP. AICAR which activates AMP-activated protein kinase (AMPK) and inhibits mTOR signaling, also markedly upregulated POX and increased POX-dependent ATP production, further supporting the role of POX during nutrient/ energy stress.

Nutrient stress not only activates pathways that conserve energy for survival, but also will provide a switch to apoptosis when a critical point is reached. We studied the generation of ROS and induction of apoptosis and found that only when nutrients were very low would ROS generation be induced leading to apoptosis. This suggested that POX activity may contribute to ROS as well as ATP. Therefore, we propose that the induced POX activity, once the stress exceeds the possibility of survival, will be the source of electrons for ROS. Thus, the induced degradation of proline under conditions of stress may contribute to maintaining energy levels for survival, but this can be switched from a survival to an apoptotic mode by inducing ROS along with ATP.
Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia
Authors: Jamilé Hazan, Nùria Fonknechten, Delphine Mavel, Caroline Paternotte, Delphine Samson, François Artiguenave, Claire-Sophie Davoine, Corinne Cruaud, Alexandra Dürr, Patrick Wincker, Philippe Brottier, Laurence Cattolico, Valérie Barbe, Jean-Marc Burgunder, Jean-François Prud'homme, Alexis Brice, Bertrand Fontaine, Roland Heilig, Jean Weissenbach
Journal: Nature Genetics (1999)
Abstract 18643: Role for RUNX2 in Pulmonary Arterial Hypertension
Authors: Grégoire Ruffenach, Sophie Chabot, Sandra Breuils-Bonnet, Pasquale Ferraro, Steeve Provencher, Sébastien Bonnet
Journal: Circulation (2014)

Introduction: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced pulmonary artery smooth muscle cells (PASMC) proliferation, calcification and suppressed apoptosis. Numerous biological pathways have been implicated in the sustainability of this phenotype, including P53/P21, Bcl-2 along with the STAT3/NFAT axis. Several studies have demonstrated that miR-204 is downregulated in PAH. Interestingly, miR-204 directly regulates the expression of the transcription factor RUNX2, which is implicated in many features characterizing PAH, including modulation of the BMPR2, P53/P21, and Bcl2 pathways. Hypothesis: Thus, we hypothesized that a miR-204 dependent upregulation of RUNX2 in PAH promotes PASMC proliferation, resistance to apoptosis and calcification. Methods/Results: Using human explanted lungs, fresh distal PAs and freshly isolated PASMC from both control and PAH patients (n=5 to 12), we demonstrated a significant (p&lt;0.05) upregulation of RUNX2 (RT-qPCR, western blot and immunofluorescence) in PAH compared to controls. Gain and loss functions experiments in PASMC showed that downregulation of miR-204 in control PASMC increases RUNX2 expression, while increases in miR-204 in PAH-PASMC decreases it (n=3 to 5 p&lt;0.05). Increased RUNX2 expression was associated with a downregulation of P53/P21 and an upregulation of Bcl2 (n=3 to 8 p&lt;0.05). More importantly, restoring miR-204 or decreasing RUNX2 expression decreased calcification (red alizarin), proliferation (Ki67) and resistance to apoptosis (TUNEL) in human PAH-PASMC (n=3 p&lt;0.05), while upregulating RUNX2 in control PASMC using an adenovirus mimicked PAH phenotype (n=3 p&lt;0.05). Finally, in Sugen/hypoxia rat model of PAH, nebulization of RUNX2 siRNA (n=15) decreased mean PA pressure, pulmonary vascular resistance, and increased exercise tolerance and cardiac output (p&lt;0.05). Conclusions: Taken together, our study uncovers a new miR-204-RUNX2 axis contributing to a P53/P21-dependent pro-proliferative and Bcl2-dependent anti-apoptotic phenotype in PAH-PASMC.