tbuckley/cabot-search huggingface dataset:
Pollutants and asthma: role of air toxics.
Authors: David B Peden
Journal: Environmental Health Perspectives (2002)

Asthma is a disease characterized by intermittent bronchoconstriction due to increased airway reactivity to both allergic and nonallergic stimuli. Most asthma exacerbations that result in hospitalization are associated with viral upper respiratory tract infections. Such infections typically induce T-helper type 1 (T(H)1) responses in the airway, involving activation of nuclear factor-kappaB (NF-Kappa B). However, a more recently appreciated cause of asthma exacerbation is exposure to pollutants, including ozone and various components of particulate matter (PM), including transition metals, diesel exhaust, and biologicals such as endotoxin. Although the role of air toxics in asthma pathogenesis remains incompletely examined, many components of PM that are active exacerbants of asthma are also prominent air toxics (metal ions and organic residues). These agents have been observed to activate NF-Kappa B. Reviewed in this article are the actions of specific air pollutants on airway inflammation in humans and potential common response pathways for ozone, PM, and several air toxics.
792. Dynamic High Capacity MUSTANG® Q Membrane Units for Scaleable Anion Exchange Chromatography Purification of Adenoviral Vectors
Authors: Robert H. Kutner, Ajay Lajmi, Jakob Reiser
Journal: Molecular Therapy (2004)

Developing scaleable processes for the purification of recombinant adenoviral (rAd) vectors is essential as gene therapy advances from the laboratory to clinical trials. For gene therapy, vectors should be essentially free from all contaminants such as RNA, chromosomal DNA, serum proteins and host cell proteins. Suitable purification of substantial quantities of rAd vectors by conventional methods is limited, especially when density-gradient centrifugation is involved. We developed a simple scaleable process with a minimum number of sample handling steps for the purification of rAd vectors for gene therapy. The process utilizes the high dynamic binding capacity and well-designed flow characteristics of MUSTANG® Q membranes for chromatographic capture of intact, infectious viral particles. To measure the dynamic viral binding capacity of these anion-exchange membranes, the supernatant from DNase/RNase treated freeze-thaw lysates of rAd infected 911 cells from ten 15 cm dishes were loaded at various flow rates onto a MUSTANG® Q 13 mm Acrodisc® with a membrane volume of 0.03 ml. Fractions of the flow through were analytically quantified for rAd particles by real time PCR, also these fractions were quantified by correlation to a HPLC peak area response curve generated with an UNO Q column using purified virus. Dynamic rAd binding capacity was found to reach 10% breakthrough at 4.9E13 viral particles per milliliter of membrane volume at a flow rate of 40 membrane volumes per minute. Also, to measure the high capacity of MUSTANG® Q membranes, DNAse/RNAse treated supernatant from a freeze-thaw lysate of rAd infected 911 cells equivalent to twenty 150 cm dishes were loaded onto a MUSTANG® Q 25 mm Acrodisc® with a final constitution of 0.3 M NaCl. Elution of the viral particles was achieved by generating a linear salt gradient from 0.3 M to 0.6 M NaCl. A total of 1.1E13 viral particles were bound to the Acrodisc® and could be eluted quantitatively. The efficiency of this system is portrayed by the small amount of membrane volume needed for reliable capture of sizeable amounts of rAd from cell lysates. Also, purification of rAd vectors using membrane-based anion exchange chromatography is more cost effective than the use of traditional CsCl protocol where an ultracentrifuge is needed as opposed to the syringe adaptable MUSTANG® Q Acrodisc®.
Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone
Authors: K Doney, M Pepe, R Storb, E Bryant, C Anasetti, FR Appelbaum, CD Buckner, J Sanders, J Singer, K Sullivan
Journal: Blood (1992)
Prospective of <sup>68</sup>Ga-Radiopharmaceutical Development
Authors: Irina Velikyan
Journal: Theranostics (2014)

Positron Emission Tomography (PET) experienced accelerated development and has become an established method for medical research and clinical routine diagnostics on patient individualized basis.Development and availability of new radiopharmaceuticals specific for particular diseases is one of the driving forces of the expansion of clinical PET.The future development of the 68 Ga-radiopharmaceuticals must be put in the context of several aspects such as role of PET in nuclear medicine, unmet medical needs, identification of new biomarkers, targets and corresponding ligands, production and availability of 68 Ga, automation of the radiopharmaceutical production, progress of positron emission tomography technologies and image analysis methodologies for improved quantitation accuracy, PET radiopharmaceutical regulations as well as advances in radiopharmaceutical chemistry.The review presents the prospects of the 68 Ga-based radiopharmaceutical development on the basis of the current status of these aspects as well as wide range and variety of imaging agents.
Abstract 15996: Left-Variant Form of Slow-Fast AVNRT Requiring Ablation Along the Mitral Annulus
Authors: Kiyoshi Otomo, Kaname Takizawa, Naoto Inoue, Taiichiro Meguro
Journal: Circulation (2014)

Background: The reentry circuit of the slow-fast AV nodal reentrant tachycardia (AVNRT) has not been precisely delineated. Although conventional right-sided slow pathway ablation at the inferoseptal to midseptal tricuspid annulus (TA) or inside the coronary sinus (CS) is effective in most slow-fast AVNRT cases, rare cases of the left-variant form resistant to the conventional right-sided slow pathway ablation and requiring the left-sided ablation along the mitral annulus (MA) have been reported. Purpose: To evaluate the effects of the left-sided ablation along the MA in patients with the slow-fast AVNRT resistant to the conventional right-sided slow pathway ablation. Methods &amp; Results: In 5 out of 250 cases with the slow-fast AVNRT who underwent the slow pathway ablation, extensive right-sided slow pathway ablation at the mid to inferoseptal TA, CS ostium or inside the CS (&gt;10 applications) failed to eliminate tachycardia inducibility. In those 5 cases, the left-sided ablation along the inferoseptal to inferolateral MA with transseptal approach was performed during the sinus rhythm. In 2 cases, accelerated junctional rhythm was induced during the ablation along the MA and tachycardias were rendered non-inducible (upto one AV nodal echo beat). In other 2 cases, accelerated junctional rhythm was not induced during the ablation along the MA, but tachycardia became non-sustained (2-5 AV nodal echo beats). In the remaining one case, tachycardia still remained inducible even after extensive left-sided ablations. Conclusion: The left-variant forms of the slow-fast AVNRT were observed in 1.6% of all slow-fast AVNRT cases and the slow pathway ablation along the inferoseptal to inferolateral MA was effective for eliminating the tachycardia inducibility. The left-sided deviation of the reentrant circuit might explain the resistance to the right-sided slow pathway ablation and efficacy of the left-sided ablation along the MA in those cases.
A functional variant of SUMO4, a new IκBα modifier, is associated with type 1 diabetes
Authors: Dehuang Guo, Manyu Li, Yan Zhang, Ping Yang, Sarah Eckenrode, Diane Hopkins, Weipeng Zheng, Sharad Purohit, Robert H Podolsky, Andrew Muir, Jinzhao Wang, Zheng Dong, Todd Brusko, Mark Atkinson, Paolo Pozzilli, Adina Zeidler, Leslie J Raffel, Chaim O Jacob, Yongsoo Park, Manuel Serrano-Rios, Maria T Martinez Larrad, Zixin Zhang, Henri-Jean Garchon, Jean-Francois Bach, Jerome I Rotter, Jin-Xiong She, Cong-Yi Wang
Journal: Nature Genetics (2004)
Abstract 12514: Deletion of Angiotensin IV Receptor (AT4R) Promotes Inflammation and Accelerates Development of Angiotensin II-Induced Aortic Aneurysms
Authors: Yasushi Numaguchi, Masakazu Ishii, Manabu Niwa, Kenji Okumura, Toyoaki Murohara
Journal: Circulation (2010)

Insulin-regulated aminopeptidase (IRAP) has been identified a key regulator of MHC class I cross-presentation as well as angiotensin IV (AngIV) receptor (AT4R). We hypothesized that IRAP contribute...
Measurement of IgG Antibodies against Timothy Pollen Allergens
Authors: P. Prahl, P Skov, U. Minuva, B. Weeke
Journal: Allergy (1981)

This study describes a microtiter double antibody assay for the measurement of specific IgG, which is believed to be identical with blocking antibodies. The precipitates were harvested on glass fiber filters, and the activity from iodinated antigens fixed in the precipitates was used as a measure of the level of the serum blocking antibodies.
PERSIMMON PHYTOBEZOAR WITH CASE REPORT
Authors: James H. Mcneill
Journal: Annals of Internal Medicine (1941)

Case Reports1 May 1941PERSIMMON PHYTOBEZOAR WITH CASE REPORTJAMES H. MCNEILL, M.D., F.A.C.P.JAMES H. MCNEILL, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-11-2142 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPersimmon phytobezoar, nearly unknown in Europe, is ordinarily seen in the United States and Japan where the persimmon is native. Males, because they are more likely to eat persimmons under certain circumstances, are more frequently affected. Age seems to have no effect, cases having been reported between the ages of six and 75. Its presence is manifested within a relatively short time after ingestion of the fruit. There is, accordingly, a seasonal incidence, in the late fall and early winter, when the persimmons are ripening.Izumi, Isida and Iwamoto1defined the chemical and physical factors which combine to form the...Bibliography1. IZUMIISIDAIWAMOTO : The mechanism of the formation of phytobezoars with special reference to persimmon ball, Jap. Jr. Med. Sci. Trans., 1933, ii, 21-35. Google Scholar2. COPETTI L: Two cases of phytobezoar, Il Policlinico (Sez prat.), 1932, xxxix, 1005. Google Scholar3. ALLEN LG: Phytobezoar: report of 3 cases, Am. Jr. Roentgenol., 1938, xxxix, 67. Google Scholar4. RUTLEDGE CP: Phytobezoar of the stomach associated with gastric ulcer, New Orleans Med. and Surg. Jr., 1937, xc, 35. Google Scholar5. RODGERS FD: Phytobezoar of persimmon origin, Radiology, 1937, xxix, 494. CrossrefGoogle Scholar6. RAMSTAD NO: Phytobezoar with gastric ulcer, Journal-Lancet, 1938, lviii, 505. Google Scholar7. WYATT WS: Phytobezoar, Kentucky Med. Jr., 1932, xxx, 79. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: North Wilkesboro, North Carolina*Received for publication October 23, 1940. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPhytobezoar and gastroscopic observation 1 May 1941Volume 14, Issue 11Page: 2142-2147KeywordsFallsIngestion ePublished: 1 December 2008 Issue Published: 1 May 1941 PDF downloadLoading ...
Abstract 11552: Statin Therapy in Patients With Type 2 Diabetes: Development and Validation of a Model to Predict Individualized Treatment Effects Based on the ASCOT, ALLHAT and CARDS Trials
Authors: Lotte Kaasenbrood, Neil R Poulter, Peter S Sever, Helen Colhoun, Shona J Livingstone, Sara L Pressel, Barry R Davis, Yolanda van der Graaf, S. Matthijs Boekholdt, Frank L Visseren
Journal: Circulation (2014)

Introduction: Clinicians need to translate results from randomized clinical trials to individual patients with type 2 diabetes mellitus (T2DM). In this study we aim to develop and validate a model for the prediction of absolute risk reductions (ARR) for major cardiovascular events by usual-dose statin therapy for individuals with T2DM. Methods: Data from the ASCOT-LLA trial (atorvastatin 10 mg versus placebo) of 2,725 T2DM patients were used to predict 10-year individualized ARR on major cardiovascular events (myocardial infarction, stroke or cardiovascular death). Predictions were based on a newly developed model of 8 predictors: age, sex, current smoking, systolic blood pressure, non-HDL cholesterol, fasting glucose, history of cardiovascular events and treatment allocation (statin or placebo). External validation was performed in ALLHAT-LLT (3,878 T2DM patients) and CARDS (2,838 T2DM patients). Possible effect modification of statin therapy was evaluated for baseline cardiovascular risk and single interactions between predictors and treatment allocation. Results: The predicted 10-year ARR for cardiovascular events was low (&lt;2%) for 13% of the T2DM patients, translating in 10-year NNT &gt;50 (Figure 1). About 30% of the T2DM patients had an ARR of &gt;4% (10-year NNT &lt;25). The addition of treatment interactions did not significantly improve model performance. The developed model showed adequate calibration and moderate discrimination in both external validation sets (concordance statistic 0.64 in ALLHAT and 0.68 in CARDS). Conclusion: Absolute risk reductions by statin therapy can be estimated for individual patients with T2DM using a model based on trial data. There is a wide distribution in absolute risk reduction by statin therapy in T2DM patients due to a distribution in cardiovascular risk. Individualized treatment effects are more informative for patients and clinicians than relative average effects and can be used to guide clinical decision-making.
Abstract P2-05-09: Functional mapping of the oncogenic kinome activity of triple-negative breast cancer cells
Authors: Bo Pan, Miki Mori, Pei Rong Evelyn Lee, Marij Hartog, Qiang Sun, Laura van 't Veer, Jean-Philippe Coppe
Journal: Cancer Research (2015)

Abstract Background: Triple-negative breast cancer (TNBC) accounts for approximately 10 to 15% of all breast cancer cases. The management of TNBC cases will significantly improve once molecular mechanisms specific to TNBC cells will be identified and treated accordingly. Evidence suggests that TNBC cells display deregulated kinase-dependent signaling cascades that differ from non-triple-negative breast cancer cells. We hypothesized that uniquely divergent phospho-circuits could be distinguished between TNBC and non-TNBC cell lines. By revealing such unique, dysfunctional phospho-signaling network, our long-term objective is to identify kinases that underpin triple-negative breast cancer development, and can be inhibited using targeted therapy. Methods: The kinome activity of TNBC and non-TNBC cell lines was identified (HCC70, MDA-MB-231, MDA-MB-436 compared to AU565, MCF-7, T47D). The functional phospho-signature of each breast cancer cell was analyzed using a high throughput experimental platform that monitors the level of activity of myriad kinases at once. This technique uses 242 phospho-sensing probes and 78 controls in an aqueous-based assay to simultaneously and directly measure the phospho-catalytic activity of phosphorylating enzymes in cell lysates. We mapped the most significantly deranged phospho-signaling cascades and the related kinases. Results: Using 6 cell lines tested under various conditions, we generated 72 phospho-signatures, out of a total of 23,040 data points. After validating the repeatability and robustness of the assay, the kinase activity signature of each breast cancer cell line was analyzed and compared to each other using unsupervised hierarchical clustering. The phospho-sensing assay revealed the heterogeneity of kinase activity networks among breast cancer cells. These data also established that phospho-signaling cascades related to AKT, ERK, and SRC kinases were differentially altered in TNBC and non-TNBC cell lines. Conclusions: We successfully identified unique phospho-circuits of TNBC and non-TNBC cell lines. Our goal is now to test whether specific kinase inhibitors can efficiently kill or prevent the growth of TNBC cell lines in culture and animal models. We will expand our approach into a high-content, functional kinome-screening platform to characterize the phospho-fingerprint of breast cancer cells and tissues, and explore the druggable, kinase-dependent mechanisms critical to triple-negative breast tumors. Citation Format: Bo Pan, Miki Mori, Pei Rong Evelyn Lee, Marij Hartog, Qiang Sun, Laura van 't Veer, Jean-Philippe Coppe. Functional mapping of the oncogenic kinome activity of triple-negative breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-05-09.
363. Uptake and Intracellular Trafficking of Stabilized and Unstabilized Gene Delivery Particles
Authors: Swaroop Mishra, Paul Webster, Mark E. Davis
Journal: Molecular Therapy (2004)

The intracellular trafficking of gene delivery particles has primarily been studied using delivery vehicles that are not formulated for in vivo conditions. Stabilized particles appropriate for in vivo use may be processed differently than the unstabilized analogues. To address this issue, we have used transmission electron microscopy to examine the uptake and intracellular trafficking of stabilized and unstabilized polyplexes. We have used polyplexes prepared with plasmid DNA (pDNA) and either branched polyethylenimine or a linear, β-cyclodextrin-containing polycation. For both polycations, unstabilized polyplexes aggregated in solution and entered cells as large aggregates. Polyplexes stabilized by addition of poly(ethylene glycol), however, produced salt-stablized particles that were observed as discrete entities within cells. Immunolabeling with colloidal gold markers demonstrated the intracellular distribution of polyplexes and the presence of intracellular, unpackaged polyplex components in both the cytoplasm and the nucleus of cells.
Quality Improvement Organizations and the Institute of Medicine—Reply
Authors: Claire Snyder
Journal: JAMA (2005)

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
A Bipolar Theory of Living Processes.
Authors: George W. Crile, Amy F. Rowland
Journal: JAMA (1926)

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
Abstract 16404: CETP Inhibitor K-312 Lowers PCSK9 Expression and LDL Cholesterol Levels in vivo
Authors: Katsutoshi Miyosawa, Sasha Singh, Yuichiro Watanabe, Haruki Shibata, Ken Mizuno, Sohei Tanabe, Masanori Aikawa
Journal: Circulation (2014)

Background: Despite potent LDL-cholesterol (LDL-C) therapies, substantial residual cardiovascular risk remains. Proprotein convertase subtilisin/kexin 9 (PCSK9) is a promising target for lowering LDL-C. We recently demonstrated that K-312, originally found as a cholesteryl ester transfer protein (CETP) inhibitor, decreased PCSK9 expression in vitro through the reduction of its promoter activity. The present study has further examined the underlying molecular mechanisms and in vivo effects of K-312 on PCSK9 levels using mass spectrometry. Methods and Results: CETP silencing by siRNA in the human hepatocyte cell line HepG2 did not compromise suppression of PCSK9 expression by K-312, indicating a mechanism independent of CETP inhibition. Transcription factors sterol-regulatory element binding protein (SREBP)-1 and SREBP-2 bind to the sterol regulatory element (SRE) of PCSK9 promoter when their precursor forms are cleaved into active forms. K-312 treatment decreased binding of SREBP-1 and SREBP-2 to SRE of the PCSK9 promoter (chromatin immunoprecipitation) and active forms of SREBP-1 and SREBP-2 (western blotting), suggesting the suppression of PCSK9 expression by K-312 involves SREBP-1 and SREBP-2. We then examined the effects of K-312 in cholesterol-fed New Zealand White rabbits administered either vehicle (N=7) or K-312 30 mg/kg (N=7) for 2 weeks. K-312 treatment decreased LDL-C (vehicle: 272.5 ± 42.2 mg/dl; K-312: 193.0 ± 36.5 mg/dl), increased HDL cholesterol (vehicle: 29.9 ± 3.7 mg/dl; K-312: 93.3 ± 14.7 mg/dl) and decreased PCSK9 mRNA levels in the liver by 63%. We further used two mass spectrometry-based approaches to measure PCSK9 levels in rabbit plasma: spectral counting and a novel high resolution (HR)-MS/MS quantification method. Immunoprecipitation of PCSK9 successfully enriched PCSK9 signal. Spectral counting and HR-MS/MS of PCSK9 peptides both demonstrated that K-312 treatment significantly decreased plasma PCSK9 levels by 76% (p&lt;0.01) and 60% (p&lt;0.05), respectively. Conclusion: K-312 may lower LDL cholesterol levels by suppressing CETP activity and PCSK9 expression, serving as a novel therapy for dyslipidemia and cardiovascular disease.