tbuckley/cabot-search huggingface dataset:
Abstract 1251: Lipophilic Index of Fatty Acid Fluidity in Erythrocyte and Plasma and Risk of Coronary Heart Disease
Authors: Eric L Ding, Qi Sun, Hannia Campos, Frank B Hu
Journal: Circulation (2008)

Multiple lines of evidence suggest that fatty acid (FA) binding affinity, viscosity, and cellular membrane fluidity together may play important roles in cardiovascular pathophysiology. Conventional classifications also incompletely capture the wide heterogeneity of diverse FAs. Via a novel etiologic paradigm, we investigate the Lipophilic Index (LI) and risk of coronary heart disease (CHD). Prospective nested case-control study in a cohort of 32,826 U.S. women who provided baseline blood in 1989 –1990. During 6-years follow-up, 166 incident CHD cases were matched with 327 controls. Assaying full FA profiles via gas chromatography, 43 FAs were identified in plasma and erythrocytes. We developed a novel FA risk index based on molecular properties of fat lipophilicity, constructed upon FA melting points, and parameterized via individual weighted summation of melting points; the LI was constructed upon 32 unique FAs with official melting points. Among controls, mean (SD) lipophilicity was 16.8°C (2.48) for Plasma-LI and 17.1°C (1.5) for Erythrocyte-LI, r=0.54. In prospective analyses, increasing Plasma-LI and Erythrocyte-LI were strongly associated with greater risk of CHD in both crude and multivariable models: RR=3.56 (95%CI: 1.48 – 8.67, P-trend=0.001) for Plasma-LI, and RR=3.80 (1.12–12.9, P-trend=0.03) for Erythrocyte-LI, comparing extreme quintiles. Individuals with higher LI also exhibited adverse lipid profiles, hyperglycemia, hypertension, and endothelial dysfunction. Notably, higher Plasma-LI was associated with having low HDL&lt;40mg/dl (OR per-SD=2.71, 1.91–3.84; P&lt;0.0001), elevated triglycerides&gt;=150mg/dl (OR=3.89, 2.83–5.35; P&lt;0.0001), hypertension (OR=1.34, 1.07–1.66; P=0.009), elevated HbA1c&gt;=6% (OR=1.50, 1.17–1.91; P=0.001), and highest quintile of E-selectin (OR=1.92, 1.47–2.50; P&lt;0.0001). LI trends with CHD risk also persisted after adjustment for these metabolic risk factors, plus trans and total fat intakes. The Lipophilic Index of plasma and erythrocyte fatty acids is strongly associated with adverse metabolic profiles and higher risk of CHD development. Findings support a novel mechanism that fatty acid lipophilicity is important in CHD pathogenesis.
Abstract 1797: Discovery of NVP-CGM097, a highly potent and optimized small molecule inhibitor of Mdm2 under evaluation in a Phase I clinical trial
Authors: Sebastien Jeay, Joerg Berghausen, Nicole Buschmann, Patrick Chène, Robert Cozens, Dirk Erdmann, Stéphane Ferretti, Pascal Furet, Tobias Gabriel, François Gessier, Diana Graus-Porta, Francesco Hofmann, Philipp Holzer, Moriko Ito, Edgar Jacoby, Michael Jensen, Joerg Kallen, Marc Lang, Joanna Lisztwan, Masato Murakami, Carole Pissot-Soldermann, Stephan Ruetz, Caroline Rynn, Dario Sterker, Stefan Stutz, Thérèse Valat, Marion Wiesmann, Keiichi Masuya
Journal: Cancer Research (2014)

Abstract Activation of p53 by blocking the p53-Mdm2 interaction using non-peptidic small-molecule inhibitors is being pursued as a promising cancer therapeutic strategy. In the present study, we show the identification of NVP-CGM097, a novel, highly optimized, and selective inhibitor of the p53-Mdm2 interaction. NVP-CGM097 binds to human Mdm2 protein with a Ki value of 1.3 nM, activates p53 in human cells and induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells. Its activity and selectivity has been tested and confirmed across a large panel of cancer cell lines from the Cancer Cell Line Encyclopedia. Importantly, NVP-CGM097 displays desirable pharmacokinetic and pharmacodynamic profiles in animals together with excellent oral bioavailability, which triggers rapid and sustained activation of p53-dependent pharmacodynamic biomarkers resulting in tumor regression in multiple xenografted models of p53 wild-type human cancer. The validation and understanding of its mechanism of action, the overall favorable drug-like properties and the characterization of its on-target toxicological profile in preclinical species strongly supported the initiation of Phase I clinical trials with NVP-CGM097 in pre-selected patients with p53 wild-type tumors. Citation Format: Sebastien Jeay, Joerg Berghausen, Nicole Buschmann, Patrick Chène, Robert Cozens, Dirk Erdmann, Stéphane Ferretti, Pascal Furet, Tobias Gabriel, François Gessier, Diana Graus-Porta, Francesco Hofmann, Philipp Holzer, Moriko Ito, Edgar Jacoby, Michael Jensen, Joerg Kallen, Marc Lang, Joanna Lisztwan, Masato Murakami, Carole Pissot-Soldermann, Stephan Ruetz, Caroline Rynn, Dario Sterker, Stefan Stutz, Thérèse Valat, Marion Wiesmann, Keiichi Masuya. Discovery of NVP-CGM097, a highly potent and optimized small molecule inhibitor of Mdm2 under evaluation in a Phase I clinical trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1797. doi:10.1158/1538-7445.AM2014-1797
Minimum information about a microarray experiment (MIAME)—toward standards for microarray data
Authors: Alvis Brazma, Pascal Hingamp, John Quackenbush, Gavin Sherlock, Paul Spellman, Chris Stoeckert, John Aach, Wilhelm Ansorge, Catherine A. Ball, Helen C. Causton, Terry Gaasterland, Patrick Glenisson, Frank C.P. Holstege, Irene F. Kim, Victor Markowitz, John C. Matese, Helen Parkinson, Alan Robinson, Ugis Sarkans, Steffen Schulze-Kremer, Jason Stewart, Ronald Taylor, Jaak Vilo, Martin Vingron
Journal: Nature Genetics (2001)
Detecting Acute HIV Infections Feasible, North Carolina Program Demonstrates
Authors: Rebecca Voelker
Journal: JAMA (2003)

PUBLIC HEALTH OFFICIALS IN NORTH Carolina say they are changing the face of HIV surveillance with a new, statewide testing system that uses HIV RNA screening to detect HIV infections within days or weeks after they occur. Unlike conventional HIV testing, which detects anti-HIV antibodies in the blood formed by the body weeks to months after infection, RNA screening detects the presence of the virus itself. The North Carolina Department of Health and Human Services implemented the Screening and Tracing Active Transmission (STAT) program last November after participating in a pilot program with researchers from the University of North Carolina at Chapel Hill. Findings from the pilot study showed that the addition of RNA screening to conventional antibody testing increased diagnostic yield by 10% and detected acute infections identified via antibody testing. Of 8155 individuals whose HIV antibody tests were negative, RNA screening picked up four acute infections ( JAMA. 2002; 288:216-221). “When we saw the results of the pilot, that we identified people [as HIVpositive] that we normally would have missed, we decided we needed to implement this program,” said Evelyn Foust, MPH, head of the state health department’s HIV/STD Prevention and Care Branch. North Carolina is the first state in the country to implement an RNA screening program to detect acute infections, and other states have expressed interest in it, said Christopher Pilcher, MD, professor of medicine at the University of North Carolina and lead evaluator of the STAT program. The Centers for Disease Control and Prevention (CDC) plans to announce later this year that it will award grants for the study of the feasibility of RNA screening on a wider basis. However, even though CDC officials say the program has merit, they say there are a number of unanswered questions about the use of RNA testing as a screening tool. “We have been looking at doing this in other places, but there are concerns,” said Robert Janssen, MD, director of the CDC’s division of HIV/AIDS prevention.
Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment
Authors: Jeffrey M. Drazen, Chandri N. Yandava, Louise Dubé, Natalie Szczerback, Richard Hippensteel, Antonino Pillari, Elliot Israel, Nicholas Schork, Eric S. Silverman, David A. Katz, Jeffrey Drajesk
Journal: Nature Genetics (1999)
Recommendation to Develop Strategies to Increase the Number of ST-Segment–Elevation Myocardial Infarction Patients With Timely Access to Primary Percutaneous Coronary Intervention
Authors: Alice K. Jacobs, Elliott M. Antman, Gray Ellrodt, David P. Faxon, Tammy Gregory, George A. Mensah, Peter Moyer, Joseph Ornato, Eric D. Peterson, Larry Sadwin, Sidney C. Smith
Journal: Circulation (2006)

Although evidence suggests that primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy in the majority of patients with ST-segment-elevation myocardial infarction (STEMI), only a minority of patients with STEMI are treated with primary PCI, and of those, only a minority receive the treatment within the recommended 90 minutes after entry into the medical system. Market research conducted by the American Heart Association revealed that those involved in the care of patients with STEMI recognize the multiple barriers that prevent the prompt delivery of primary PCI and agree that it is necessary to develop systems or centers of care that will allow STEMI patients to benefit from primary PCI. The American Heart Association will convene a group of stakeholders (representing the interests of patients, physicians, emergency medical systems, community hospitals, tertiary hospitals, and payers) and quality-of-care and outcomes experts to identify the gaps between the existing and ideal delivery of care for STEMI patients, as well as the requisite policy implications. Working within a framework of guiding principles, the group will recommend strategies to increase the number of STEMI patients with timely access to primary PCI.
Some Chemical Factors in Cellular Adhesion and Stickiness
Authors: Leonard Berwick, Dale Rex Coman
Journal: Cancer Research (1962)

The effects of a chelating agent, acid and alkaline phosphatase, and neuraminidase upon the mutual adhesiveness of buccal epithelial cells and upon the stickiness of these cells to siliconized glass were investigated. Stickiness to the foreign substrate was measured by a centrifugation method. Mutual adhesiveness was determined by micromanipulation. Whereas removal of calcium by disodium versenate caused a great reduction in mutual adhesiveness, it had no effect upon stickiness of the cells to the foreign substrate. Neuraminidase reduced stickiness of the cells to siliconized glass but had no effect upon mutual cellular adhesion. Acid and alkaline phosphatase reduced both stickiness and cellular adhesiveness. It is concluded that the mutual adhesiveness of these cells is dependent upon a calcium-bridge linkage between them and that at least some of this calcium is bound to phosphate groups at the cell surface. Stickiness of the cells to a foreign substrate is unaffected by calcium withdrawal and depends instead upon a soft, sticky substance that seems to be a complex containing mucopolysaccharide.
Sertraline and Depression in Children—Reply
Authors: Karen Dineen Wagner, Christopher J. Wohlberg, Ruoyong Yang
Journal: JAMA (2004)

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
Calcification of cultured urticaria pigmentosa skin.
Authors: B. HENTZER, A. OTKJAER NIELSEN, E. JOHNSON
Journal: British Journal of Dermatology (1980)

Mast cells participate in experimental calcinosis. Skin from patients with urticaria pigmentosa (cutaneous mastocytosis) calcifies in vitro. In the present report, the nature of the calcium deposit was studied by electron optical techniques. The cultured mast cells of urticaria pigmentosa skin were surrounded by a large number of round bodies with an average diameter of 200-300 nm. Most of the round bodies were membrane bounded, while a few contained lamellar structures. These bodies may represent matrix vesicles as seen in calcifying hard tissues and/or may be remnants of mast cell granules. The calcified deposits were located on the round bodies, collagen fibrils and elastic matrix. Electron diffraction and X-ray microanalysis demonstrated that the deposits consisted of crystalline calcium apatite.
Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib
Authors: S Jagannathan, M A Y Abdel-Malek, E Malek, N Vad, T Latif, K C Anderson, J J Driscoll
Journal: Leukemia (2015)

Although the therapeutic benefit of proteasome inhibition in multiple myeloma remains unchallenged, drug resistance inevitably emerges through mechanisms that remain elusive. Bortezomib provokes unwanted protein accumulation and the endoplasmic reticulum stress to activate the unfolded protein response (UPR) and autophagy as compensatory mechanisms that restore protein homeostasis. High-throughput screens to detect pharmacologics that modulated autophagy to enhance the anti-myeloma effect of bortezomib revealed metformin, a widely used antidiabetic agent with proven efficacy and limited adverse effects. Metformin co-treatment with bortezomib suppressed induction of the critical UPR effector glucose-regulated protein 78 (GRP78) to impair autophagosome formation and enhance apoptosis. Gene expression profiling of newly diagnosed myeloma patient tumors further correlated the hyperexpression of GRP78-encoding HSPA5 with reduced clinical response to bortezomib. The effect of bortezomib was enhanced with metformin co-treatment using myeloma patient tumor cells and the chemoresistant, stem cell-like side population that may contribute to disease recurrence. The relevance of the findings was confirmed in vivo as shown by metformin co-treatment with bortezomib that delayed the growth of myeloma xenotransplants. Taken together, our results suggest that metformin suppresses GRP78, a key driver of bortezomib-induced autophagy, and support the pharmacologic repositioning of metformin to enhance the anti-myeloma benefit of bortezomib.
Abstract 1839: LKB1 deficiency enhances sensitivity to energetic stress induced by erlotinib treatment in non-small cell lung cancer (NSCLC) cells
Authors: Young M. Whang, Serk I. Park, Irina A. Trenary, Changki Lee, Jacob M. Kaufman, David P. Carbone, Jamey D. Young
Journal: Cancer Research (2014)

Abstract The tumor suppressor LKB1 is inactivated in 20-30% of non-small cell lung cancer (NSCLC) patient tumors. Because LKB1 is the master kinase phosphorylating the energy-sensing kinase AMPK, dysregulation of the LKB1-AMPK signaling axis causes loss of cellular homeostasis in response to metabolic inhibition or external stress-induced mitochondrial insults. Erlotinib is used clinically in NSCLC patients to target mutationally activated EGFR and is known to induce mitochondrial-mediated apoptosis. We investigated the metabolic response and mitochondrial function of LKB1-deficient NSCLC cells treated with erlotinib. LKB1-deficient cells exhibited enhanced sensitivity to erlotinib treatment in vitro and in vivo despite having wild-type EGFR. We found that this enhanced response was due to altered energetic metabolism and mitochondrial dysfunction in LKB1-deficient cells, which prevents homestatic maintenance of ATP and reactive oxygen species (ROS) levels in response to erlotinib treatment. Despite negative regulation of mTOR activity by LKB1-AMPK signaling, erlotinib effectively blocked mTOR signaling in LKB1-deficient cells, resulting in inhibition of cell growth, as well as activation of apoptosis. These findings will be important for designing targeted treatments for LKB1-deficient NSCLC patient tumors harboring wild-type EGFR, which disrupt metabolic and signaling pathways known to regulate energy metabolism in these cells. Citation Format: Young Mi Whang, Serk In Park, Irina A. Trenary, Changki Lee, Jacob M. Kaufman, David P. Carbone, Jamey D. Young. LKB1 deficiency enhances sensitivity to energetic stress induced by erlotinib treatment in non-small cell lung cancer (NSCLC) cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1839. doi:10.1158/1538-7445.AM2014-1839
Humility and Clinical Trials
Authors: James Wilson
Journal: Molecular Therapy (2007)

"One must be humble when investigating clinical trial phenomena" was the advice provided by Jonathan Yewdell at a symposium on immune responses to adeno-associated virus (AAV) vectors conducted by the National Institutes of Health Recombinant DNA Advisory Committee (RAC) on 19 June 2007. The symposium was organized in response to reports of apparent immune responses in two recent AAV gene therapy trials. One of these trials used an AAV serotype 2 (AAV2) vector expressing factor IX delivered to the livers of subjects with hemophilia B.
Abstract 3868: Six1 overexpression promotes malignant progression in models of cervical and colon cancer
Authors: Hanwen Xu, Yu Zhang, Lucia Pirisi, Maria Marjorette Pena, Kim E. Creek
Journal: Cancer Research (2014)

Abstract The overexpression of Six1, a member of the Six family of homeodomain transcription factors, has been found in various human cancers, and is associated with increased tumor progression and metastasis. Previous studies in our laboratory discovered that the expression of Six1 mRNA increased during in vitro progression of human papillomavirus type 16 (HPV16) immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. The overexpression of Six1 induced Epithelial-Mesenchymal Transition (EMT) by the activation of p38 MAPK in HKc/DR. Although immortalized and resistant to serum and calcium-induced differentiation, HKc/DR are not tumorigenic. To further explore the role of Six1 in HPV16 immortalized cells we determined whether overexpression of Six1 in HKc/DR resulted in malignant conversion. We found that HKc/DR overexpressing Six1 (DR-Six1), but not HKc/DR controls (DR-Ctrl), formed squamous cell carcinomas in nude mice. Cancer stem cells are proposed to drive tumor initiation and progression; for this reason we analyzed cancer stem cell markers in DR-Ctrl and DR-Six1. We found that DR-Six1 had an increased CD24-/CD44+ population and increased aldehyde dehydrogenase 1 (ALDH1) expression as compared to DR-Ctrl, indicating a cancer stem cell-like phenotype in Six1 overexpressing cells. We then used the human cervical cancer cell line HeLa to further explore the enhanced tumorigenic and malignant properties associated with Six1 overexpression. We determined that overexpressing Six1 in HeLa increased their ability to form spheroids in vitro and increased tumor size in vivo. As an extension of this work, we investigated the role of Six1 on tumorigenesis and metastasis in colon cancer in vivo and in vitro by using the murine colon cancer cell line MC38. We found that Six1 promoted colon cancer tumorigenesis, progression and metastasis, and increased the population of cancer stem cell-like cells. Taken together, our studies demonstrate that Six1 overexpression increases the cancer stem cell-like cell population, and promotes malignant progression in models of cervical and colon cancer. Supported by grant P20MD001770 from the National Institute on Minority Health and Health Disparities. Citation Format: Hanwen Xu, Yu Zhang, Lucia Pirisi, Maria Marjorette Pena, Kim E. Creek. Six1 overexpression promotes malignant progression in models of cervical and colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3868. doi:10.1158/1538-7445.AM2014-3868
Determinants of Hydroxychloroquine Blood Concentration Variations in Systemic Lupus Erythematosus
Authors: M Jallouli, L Galicier, N Zahr, O Aumaître, C Francès, V Le Guern, F Lioté, A Smail, N Limal, L Perard, H Desmurs-Clavel, D Le Thi Huong, B Asli, J-E Kahn, J Pourrat, L Sailler, F Ackermann, T Papo, K Sacré, O Fain, J Stirnemann, P Cacoub, G Leroux, J Cohen-Bittan, J Sellam, X Mariette, B Blanchet, J S Hulot, Zahir Amoura, J C Piette, N Costedoat-Chalumeau, Aurelien Delluc
Journal: Arthritis & Rheumatology (2015)

Objective Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. Methods We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration &lt;200 ng/ml) were excluded. Results To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug–drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index ( P = 0.008), no treatment with corticosteroids ( P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations ( P = 0.017), low platelet count ( P &lt; 0.001), low neutrophil count ( P &lt; 0.001), and high estimated creatinine clearance ( P &lt; 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23–58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504–2,229 ng/ml] versus 917 ng/ml [range 208–3316 ng/ml]) ( P &lt; 0.001). Conclusion We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.