tbuckley/cabot-search huggingface dataset:
Abstract 19280: Gender Disparity in Outcomes of Myocarditis
Authors: John Cherian, David Lasorda, Raef Hajjali
Journal: Circulation (2014)

Introduction: Myocarditis is an inflammatory disorder of cardiac myocytes, which can progress to dilated cardiomyopathy and heart failure. Clinical presentation is highly variable, ranging from subclinical disease to cardiogenic shock and more often affecting men, with a male-to-female ratio of 1.5:1. Women with myocarditis typically have better long-term outcomes than men, including myocardial recovery and transplant free survival. We sought to investigate the difference in in-hospital mortality between men and woman with myocarditis.

Methods: The Nationwide Inpatient Sample (NIS), part of the healthcare cost and Utilization Project (HCUP), is the largest publicly available inpatient database designed to provide information on characteristics and outcomes of patients discharged from US hospitals. Using the NIS we identified our study population, composed of all adult patients who were admitted with a primary diagnosis of myocarditis during the calendar years 2008 to 2010.

Results: We identified 990 patients with myocarditis, 644 males and 346 females. Women on average were significantly older (48 years vs. 35 years, p <0.001) and had more comorbidities (4.3 vs. 2.7, p <0.001). Women had a significantly higher incidence of shock (13.6 vs. 6.1, p<0.001), longer hospital stays (5.8 days vs. 4.0, p = 0.023) and higher in-hospital mortality (5.2% vs. 2.5%, p = 0.029). After adjusting for pertinent covariates using logistic regression analysis, female gender remained an independent predictor of increased in-hospital mortality (p=0.023, OR=2.384 [1.126-5.048]). Number of chronic conditions also independently predicted higher in-hospital mortality (p=0.000, OR=1.309 [1.174-1.461]). Presence of hypertension exhibited a protective effect (p=0.004, OR=0.048 [0.006-0.371]).

Conclusion: In patients admitted with myocarditis, women were significantly older at presentation and had more comorbidities, but after adjusting for these clinical variables, they still had significantly higher in-hospital mortality compared to men.
<i>March Through a Swamp in Pursuit of Slaves</i>
Authors: Thomas B. Cole
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
Dissecting the antimitotic activities and cellular actions of the natural product disorazole C1
Authors: Carolyn Kitchens, Marni Tierno, Bethany Petrik, Thomas Graham, Peter Wipf, Fengfeng Xu, William Saunders, Brianne Raccor, Raghavan Balachandran, Billy Day, Celeste Reese, John Lazo
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3281 

The disorazoles are a family of 29 macrocyclic polyketides isolated from the fermentation broth of the myxobacterium Sorangium cellulosum. Disorazole A1, the major component of the fermentation, was previously found to irreversibly bind to tubulin and have cytotoxic activity at picomolar concentrations, possibly due to the highly electrophilic epoxide moiety within its structure. To test this hypothesis, we synthesized disorazole C1, a minor component that lacks the epoxide moiety and examined its cytotoxic effects. We determined that disorazole C1 was able to inhibit polymerization of purified bovine tubulin in a concentration dependent manner with an IC50 of 11.8 ±0.4 µM, which was comparable to previous reports for disorazole A1. We examined the potential binding of disorazole C1 to purified tubulin by performing competitive inhibition assays against the binding of 10 µM [3H]vinblastine or [3H]dolastatin 10. We found that 5 µM vincristine and dolastatin 10 decreased [3H]vinblastine binding to tubulin by 65%. Colchicine, which does not interact with the vinca domain on tubulin, did not inhibit the binding of [3H]vinblastine, as expected. Disorazole C1 (5 µM) inhibited [3H]vinblastine binding by 50%. We also found that 5 µM vinblastine, vincristine, and disorazole inhibited the binding of [3H]dolastatin 10 by 5, 21, and 33 %, respectively. Colchicine did not disrupt [3H]dolastatin 10 binding. These results suggest that disorazole C1 does bind to tubulin and its binding site may overlap with the vinca domain. We then treated A549 cells with IC50 concentrations of disorazole C1 and found that, compared to vehicle control, cells treated with disorazole C1 had completely disrupted microtubules by 72 hours similar to that seen with IC50 concentrations of vinblastine. The multidrug resistant cell line DC3F-VCRd-5L was not cross-resistant to disorazole C1 relative to its wild-type counterpart DC3F. We attempted to develop a disorazole C1-resistant A549 lung cancer cell line using chronic treatment with low concentrations of disorazole C1. Although we were unsuccessful, we observed that the surviving cells exhibited an irreversible senescent phenotype. Studies with other microtubule disrupting agents support the hypothesis that microtubule disruption, like other mechanisms of cellular stress, can induce premature cellular senescence.
358. Route of Administration of sec-R Targeted Compacted DNA Influences Both the Site of Expression and Host Immune Response to the Vector
Authors: Assem G. Ziady, John Kim, Joseph Colla, Pamela B. Davis
Journal: Molecular Therapy (2004)

DNA can be condensed, using poly-L-lysine, under high salt conditions, into discrete unimolecular (with respect to DNA) particles, 12–30 nm in diameter. We have shown that modification of these complexes with a peptide ligand (C105Y) that binds the serpin enzyme complex receptor (sec-R) targets them to lung, liver and spleen after intravenous administration and to airway epithelial cells after intratracheal administration in mice. The receptor is present on the apical surface of airway epithelia in mice and humans. We tested the effect of different routes of administration, luminal or intravenous (IV), on host antibody response to vector and delivery of a secreted protein, Factor IX, into the blood. C57BL/6 mice (n = 10) received a transtracheal application of a 50 μl bolus of a 0.5 M NaCl solution containing 5 μg of sec-R targeted compacted pCMV FIX plasmid (codes for secretable human Factor IX driven by the CMV promoter). Control groups included animals that received 5 μg non-targeted compacted pCMV FIX in 0.5 M NaCl (n = 5), 0.5 M NaCl alone (n = 5), and 5 μg sec-R targeted pCMV FIX injected intravenously via the tail vein (n = 10). Blood was sampled on days 2, 10, and 28. Human Factor IX was detected only in the plasma of animals that received sec-R targeted complexes. The luminal application group achieving expression levels of 65–90 ng/ml plasma while the IV group achieved 59–145 ng/ml plasma. Expression persisted for 10 days but diminished by 28 days, which may be due in part to development of anti-Factor IX-antibodies. When the complexes were administered IV (n = 36), 19 of 36 immuno-competent mice dosed with sec-R targeted human Factor IX, following initial dosing with sec-R targeted lac Z complexes 3 weeks earlier, developed antibodies against the vector by 28 days, but the antibodies did not affect the efficacy of re-administration. Animals treated with saline alone or non-targeted complexes did not produce antibodies to targeted complexes. When luminal administration was used, no antibody response is observed even in animals that receive targeted complexes. In conclusion, compacted DNA, targeted to the sec-R, is effective in delivering genes in vivo following luminal or intravenous administration. The route of administration influences both the site of expression as well as the production of antibodies against the complex. Furthermore, luminal administration achieves levels of secreted protein expression and delivery to the blood comparable to what is achieved by the intravenous route.
Abstract 3612: Effect of cancer associated fibroblast on gastric cancer cells under hypoxia
Authors: Haruhito Kinoshita, Masakazu Yashiro, Go Masuda, Hiroaki Kasashima, Tamami Morisaki, Tatsunari Fukuoka, Masatune Shibutani, Sadaaki Yamazoe, Katsunobu Sakurai, Hisashi Nagahara, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2014)

Abstract Background: Cancer-associated fibroblasts (CAF) have been suggested to be associated with the scirrhous gastric cancer (SGC) progression. SGC have a heterogeneously hypoxic environment which has been currently considered to be associated with aggressive tumor phenotypes cancer. Stromal cell-derived factor (SDF)-1 and C-X-C chemokine receptor type 4 (CXCR4) form an important chemokine/receptor pair, and are supposed to be up-regulated by hypoxia inducible factor-1 (HIF-1). The aim of our study was to clarify the effect of hypoxic environment on the CAF and CXCR4/SDF-1 axis in SGC. Experimental Design: Proliferation of SGC cells grown in monoculture and co-culture with CAF under hypoxia. SGC and CAF expression level of CXCR4 and SDF-1 under hypoxia were examined by RT-PCR and ELISA. Proliferation and migration of SGC cells with SDF-1 or hepatocyte growth factor (HGF) or conditioned medium from CAF under hypoxia, furthermore, added c-Met inhibitor or CXCR4 inhibitor. Results: The proliferation that co-culture of SGC cells with CAF was significantly increased under hypoxia. The expression level of CXCR4 mRNA was significantly increased under hypoxia in all of SGC cells. SDF-1 concentration level was significantly increased under hypoxia. The proliferation of SGC cells with SDF-1 and CAF was significantly increased. The proliferation of SGC cells with CAF was inhibited by CXCR4 inhibitor under hypoxia. The migration of SGC cells with HGF and CAF was significantly increased. The migration of SGC cells with CAF was inhibited by c-Met inhibitor. Conclusion: CAF might up-regulate the proliferation and migration of SGC cells under hypoxia, in comparison with that under normoxia. CXCR4/SDF-1 axis might play an important role for the proliferation of SGC cells under hypoxia. Citation Format: Haruhito Kinoshita, Masakazu Yashiro, Go Masuda, Hiroaki Kasashima, Tamami Morisaki, Tatsunari Fukuoka, Masatune Shibutani, Sadaaki Yamazoe, Katsunobu Sakurai, Hisashi Nagahara, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. Effect of cancer associated fibroblast on gastric cancer cells under hypoxia. [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 3612. doi:10.1158/1538-7445.AM2014-3612
Age-Related Macular Degeneration
Authors: Sharon Parmet, Cassio Lynm, Richard M. Glass
Journal: JAMA (2006)

A ge-related macular degeneration (AMD) is a disease of the eye that is the leading cause of blindness for people aged 65 years and older and affects more than 10 million Americans.AMD is caused by a deterioration of the retina-the layer of the eye that contains cells that relay images through the optic nerve to the brain.The center of the retina is called the macula and is responsible for the detailed central vision that allows people to read, drive, and recognize faces.If the macula starts to break down, areas in the center of the visual field start to look blurred.Risk factors for AMD include older age, white race, and smoking.There is no cure for AMD, but therapies are available that can slow the disease.The May 24/31, 2006, issue of JAMA includes an article on age-related macular degeneration.This Patient Page is based on one previously published in the November 19, 2002, issue of JAMA.
US takes precautions against BSE
Authors: Fred Charatan
Journal: BMJ (2001)

Health officials in the United States have been taking stringent precautions to prevent bovine spongiform encephalopathy (BSE). Imports of beef and bovine products are banned, and no one who has lived in the United Kingdom since the late 1980s, when the BSE epidemic first became known, is allowed to donate blood.

So far, no cases of BSE have been identified in US cattle, although the related diseases of scrapie in sheep and chronic wasting disease in elk and deer have been spreading. It is not known whether eating infected sheep, deer, or elk causes any …
Abstract 11866: Left Ventricular Diastolic Function Assessed by Echocardiography and Tissue Doppler Imaging is a Strong Predictor of Cardiovascular Events in Patients With Diabetes Mellitus Type 2
Authors: Peter Blomstrand, Martin Engvall, Karin Festin, Torbjorn Lindstrom, Toste Lanne, Eva Maret, Fredrik Nystrom, John Ouda, Carl-Johan Ostgren, Jan E Engvall
Journal: Circulation (2014)

Aims: The aim of the study was to evaluate the independent role of left ventricular systolic function in terms of global longitudinal strain, and diastolic function expressed as the ratio between early diastolic transmitral flow- and mitral annular motion velocities (E/é) in predicting cardiovascular events in patients with diabetes mellitus type 2. Methods: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, carotid intima media thickness, carotid-femoral pulse wave velocity, pulse pressure measurement (pp) and glycosylated hemoglobin (HbA1c) were analysed. Results: Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 ± 17 months. Univariate Cox regression analysis showed that E/é was a strong predictor of cardiovascular events (HR 1.12; 95 % CI 1.06 to 1.18, p &lt; 0.001) and in a multivariate analysis E/é was prospectively associated with cardiovascular events independent of age, sex, global longitudinal strain, pulse wave velocity, carotid intima media thickness, pp and HbA1c. The addition of HbA1c and pp to E/é increased the predictive value of the model significantly, [(E/é vs. E/é + HbA1c vs. E/é + HbA1c + pp) χ 2 = 18.1 vs. χ 2 = 23.0 vs. χ 2 =30.0, p = 0.030 vs. p = 0.007], but global longitudinal strain did not. An elevated E/é ratio, defined as &gt; 15, was also predictive of major cardiovascular events in a Kaplan-Meyer analysis. The cumulative probability of the development of an event during the follow-up period for patients with an E/é ratio &gt; 15 was 8.6 % compared with 2.6 % for patients E/é ratio ≤ 15, p = 0.021. Conclusion: Left ventricular diastolic dysfunction expressed as E/é is a strong predictor of myocardial infarction and stroke in middle-aged patients with diabetes mellitus, superior to global longitudinal strain, arterial stiffness and carotid intima media thickness.
Abstract 15990: Disturbed Shear Stress Facilitates Caveolae-Mediated oxLDL Uptake Leading to Increased Endothelial Stiffness
Authors: Elizabeth LeMaster, Shan Sun, David Eddington, Michael Cho, Richard Minshall, Irena Levitan
Journal: Circulation (2014)

Introduction:  Oxidized low density lipoprotein (oxLDL) is a key risk factor in the formation of atherosclerotic plaques, which are primarily located at vessel bifurcations that exhibit bidirectional recirculating disturbed shear stress (DSS) patterns. It is also well known that while DSS patterns are pro-atherogenic, laminar shear stress (LSS) is atheroprotective.   Hypothesis:  OxLDL uptake into endothelial cells (ECs) is caveolin-1 (Cav-1) protein dependent and increases under DSS conditions leading to increased cellular stiffness.   Methods:  To address these questions, a microfluidic channel with a step barrier was designed, tested and fabricated to generate both unidirectional LSS and recirculating DSS patterns onto an endothelial monolayer for 48 hours. EC stiffness was assessed using atomic force microscopy.   Results:  Our results show a 40% increase in endothelial oxLDL uptake in DSS vs. LSS regions (n=4, p ex vivo  stiffness measurements of intact vessels from wild type (WT) mice which showed a 50% increase in EC stiffness in the DSS regions of the aortic arch as compared to the LSS regions of the descending aorta (DA) (n=5, p   Conclusion:  Taken together, this study suggests that DSS-induced increase in oxLDL uptake is mediated by caveolae and plays a significant role in increasing localized EC stiffness which in turn is expected to impair endothelial barrier function.
The influence of the tumor microenvironment on drug response and drug resistance
Authors: William Dalton
Journal: Clinical Cancer Research (2008)

PL04-03   Drug resistance remains a major obstacle to prolonging the lives of cancer patients. Recently, investigators have become more aware of the influence of the tumor microenvironment on tumor cell survival and growth. Hematological malignancies serve as a model for studying tumor-microenvironment interactions using the bone marrow as the primary microenvironment factor. The central hypothesis is that the bone marrow microenvironment provides a sanctuary for subpopulations of malignant cells to evade or circumvent drug-induced death and that this represents a form of  de novo  drug resistance.  We use the term “environment-mediated drug resistance or EMDR” to describe the combination of mechanisms that contribute to this form of  de novo  drug resistance. By definition,  de novo  drug resistance is associated with conditions that protect cells from initial drug exposure and therefore are present during drug selection. EMDR includes a combination of soluble factors and cell contact, and can be subdivided into soluble factors - mediated drug resistance, and cell adhesion mediated drug resistance. We propose that the tumor microenvironment protects tumor cells from drug-induced stress and cell death by two primary mechanisms: (a) a paracrine mechanism due to soluble cytokine and/or growth factors produced as a result of the tumor cell: environment interaction, and (b) a physical contact mechanism referred to as “cell adhesion-mediated drug resistance,” (CAM-DR). This protection allows tumor cells to survive the insult of chemotherapy, leading to minimal residual disease (MRD), and thereby increases the probability for the development of acquired drug resistance. Targeting the microevironment for new drug discovery provides a unique approach to improving treatment outcomes for hematological malignancies, and possibly other cancers. Interrupting tumor cell: bone marrow microenvironment interaction and/or signal transduction mechanisms associated with these interactions represents a novel approach to enhancing treatment effect and improving patient outcomes.
Engraftment, clinical, and molecular follow-up of patients with multiple myeloma who were reinfused with highly purified CD34+ cells to support single or tandem high-dose chemotherapy
Authors: Roberto M. Lemoli, Giovanni Martinelli, Elena Zamagni, Maria Rosa Motta, Simonetta Rizzi, Carolina Terragna, Roberto Rondelli, Sonia Ronconi, Antonio Curti, Francesca Bonifazi, Sante Tura, Michele Cavo
Journal: Blood (2000)
Abstract 15090: Upregulation of Cxcr4 Gene Expression Enhances in vivo Reendothelialization of Human Endothelial Progenitor Cells
Authors: Jun Tao, Long Chen, Zhen Yang
Journal: Circulation (2010)

Background: Endothelial progenitor cells (EPCs) play a pivotal role in endothelial repair after artery injury. The chemokine receptor CXCR4 is a key modulator of EPCs homing to impaired artery and ...
Meeting highlights from the 2013 <scp>E</scp>uropean <scp>S</scp>ociety of <scp>C</scp>ardiology <scp>H</scp>eart <scp>F</scp>ailure <scp>A</scp>ssociation <scp>W</scp>inter <scp>M</scp>eeting on <scp>T</scp>ranslational <scp>H</scp>eart <scp>F</scp>ailure <scp>R</scp>esearch
Authors: Mathias Hohl, Hossein Ardehali, Francisco J. Azuaje, Ross A. Breckenridge, Wolfram Doehner, Philip Eaton, Georg B. Ehret, Toshiro Fujita, Roberto Gaetani, Mauro Giacca, Gerd Hasenfuß, Stephane Heymans, Adelino F. Leite‐Moreira, Wolfgang A. Linke, Dominik Linz, Alexander Lyon, Mamas A. Mamas, Matej Orešič, Zoltán Papp, Thierry Pedrazzini, Massimo Piepoli, Benjamin Prosser, Rosario Rizzuto, Guido Tarone, Rong Tian, Emeline van Craenenbroeck, Eva van Rooij, Timothy Wai, Günter Weiss, Christoph Maack
Journal: European Journal of Heart Failure (2013)