tbuckley/cabot-search huggingface dataset:
Abstract 912: Spleen Tyrosine Kinase Regulates TLR4 dependent Macropinocytosis And Lipid Accumulation In Macrophages
Authors: Soo-Ho Choi, Felicidad Almazan, Yury I Miller
Journal: Circulation (2007)

Toll-like receptors play a key role in the signaling pathways of innate immune response and have been recently shown to contribute to vascular inflammation and atherosclerosis. Oxidation of LDL is considered a leading mechanism of atherogenesis, and in our previous studies, we demonstrated that minimally modified LDL (mmLDL) induced TLR4-dependent chemokine secretion as well as robust actin polymerization and spreading of macrophages. We noticed that these mmLDL-induced cytoskeletal rearrangements led to extensive vacuolization, characteristic of macropinocytosis. In this study, we examined the mechanisms of TLR4-induced actin polymerization and macropinocytosis. It has been reported that spleen tyrosine kinase (Syk) regulates actin cytoskeleton and that it may interact with TLR4. We found in the immunoprecipitation experiments that mmLDL induced Syk association with TLR4 as well as Syk phosphorylation. Next we developed a J774 macrophage cell line, which stably expressed Syk shRNA and had the Syk expression reduced by 70% or more. Using this Syk-deficient macrophage cell line and specific Syk inhibitors, we demonstrated that Syk is necessary for mmLDL-induced activation of Ras and phosphorylation of Raf-MEK1-ERK1/2. The ERK1/2 activation resulted in phosphorylation of paxillin and an increase in the formation of N-WASP/Arp2 complex, which initiates actin polymerization. Taken together, these results suggest that Syk is a critical kinase in the mmLDL macrophage activation and that the mmLDL-induced cytoskeleton signaling. In addition, we demonstrated that mmLDL induced macrophage uptake of native LDL and of fluorescent 10 KDa dextran, and that this effect was Syk-dependent. These data suggest a novel pathway for the mmLDL-induced macropinocytosis in macrophages, which may constitute a mechanism for macrophage lipid accumulation and foam cell formation, a characteristic step in the development of atherosclerosis.
Identification of supportive care needs in a sample of Puerto Rican cancer patients with the Supportive Care Needs Survey-34 (SCNS-34)
Authors: V. Gonzalez, M. Velez, E. Pedro, C. Cruz, M. Cotto, M. Colon, J. Romaguera, C. Chevere-Mourino, L. A. Delgado- Mateu, M. Tirado-Gomez
Journal: Journal of Clinical Oncology (2009)

e20697 Background: The assessment of supportive care needs is important in the management of cancer patients. The Supportive Care Needs Survey (SCNS-34) was administered to a population of Puerto Rican cancer patients to assess their perceived needs in five domains (psychological, health system and information, physical and daily living, patient care and support, and sexuality.) Methods: Patients attending the surgical, radiation and medical oncology clinics at the Puerto Rico Medical Center participated in the study. After informed consent, patients completed the Spanish- Puerto Rican translation of the SCNS-34. A second instrument to measure the quality of the SCNS-34 was administered. Demographic and clinical data was obtained from medical records. Descriptive, univariate and multivariate analysis was performed to assess correlation between reported needs and demographic and clinical data. To assess the validity and consistency of the Spanish Puerto Rican translation of the SCNS-34, the Cronbach's alpha test was used. Results: A total of 103 patients participated in the study (female n=66; male n=37). Median age was 54 years. The most common malignancies were breast cancer (29 patients), gynecologic cancers (22 patients), prostate cancer (17 patients) and gastrointestinal cancers (14 patients). The overall internal consistency of the instrument was 0.882. Patients perceived needs were highest in the domains of sexuality (67%), physical and daily living (55.3%), and psychological (38.8%). Logistic regression analysis demonstrated that younger age was an independent predictor of perceived needs in the psychologic domain (p=0.010). Also, a diagnosis of breast cancer was a significant predictor of perceived needs in the health system and information domain (p=0.020). Being a female was correlated with reporting needs in the domain of physical and daily living (p=0.009). Educated patients were more prone to perceive needs in the domains of sexuality (p=0.045). Conclusions: The Spanish- Puerto Rican translation of the Supportive Care Needs Survey (SCNS-34) showed satisfactory internal consistency and validity. The supportive care needs of Puerto Ricans cancer patients seem to be affected by age, gender, and cancer site. No significant financial relationships to disclose.
Abstract 20076: Effect of Combination Therapy with Benazepril/Amlodipine Compared with Benazepril/Hydrochlorothiazide in Patients with High-Risk, Stage 2 Hypertension with or Without Known Coronary Artery Disease
Authors: Bertram Pitt, Kenneth Jamerson, Michael A Weber, Matthew R Weir, Roxzana Y Kelly, Allen Hester, Tsushung A Hua, Dion Zappe, Björn Dahlöf, Eric J Velazquez, George L Bakris
Journal: Circulation (2010)

Combination therapy with benazepril 40 mg/amlodipine 10 mg (B+A) has been shown to be more effective than benazepril 40 mg/HCTZ 25 mg (B+H) in reducing cardiovascular (CV) events in high risk patients (pts) with stage 2 hypertension (HTN) at equivalent blood pressure (BP) reduction. While patients with angina or recent CV events were excluded from the study the known effectiveness of amlodipine in pts with coronary artery disease (CAD) prospectively raised the question as to whether B+A would be more effective than B+H in reducing CV events in pts without known CAD (non CAD) at baseline. At baseline there were significant differences between the 5314 CAD and the 6191 non CAD pts. CAD pts had lower SBP and pulse, less stroke and diabetes, more dyslipidemia and more on lipid-lowering agents, beta-blockers and anti-platelets. However, there were no differences at baseline between B+A and B+H in either the CAD or non CAD pts. In pts with CAD the mean BP for B+A and B+H was 143.9 and 144.2 mmHg (146.5 and 146....
Abstract 12108: Long-term Follow-up of Patients with Permanent Pacemaker Implantation after Cardiac Surgery
Authors: Syed S Raza, Mackenzie Mbai, Ranjit John, Jian-Ming Li, Venkatakrishna Tholakanahalli, Selcuk Adabag
Journal: Circulation (2010)

Background:  Each year approximately 20,000 patients (pts) undergo permanent pacemaker (PPM) implantation postoperatively after cardiac surgery for bradycardia or atrioventricular block. However, the long-term follow-up of these pts is lacking. The objective of this investigation was to examine the long-term outcomes of pts who underwent postoperative PPM implantation after cardiac surgery.   Methods:  We included 6,268 consecutive pts who underwent cardiac surgery at the Minneapolis Veterans Administration Medical Center between 1987 and 2010. Pts who had a PPM implantation within 30 days of cardiac surgery were identified from cardiology and surgery databases. Pacemaker interrogation results and dependence status were obtained from device clinic records. Predictors of PPM implantation was examined by logistic regression and long-term survival by Cox regression.   Results:  Mean age was 66±10 and 75% of pts had isolated coronary artery bypass surgery (CABG). Overall, 141 (2.2%) pts underwent PPM implantation 9±6 days after surgery. PPM was required in 1% of pts after CABG, 6%–8% of pts after mitral or aortic valve replacement and 14%–17% of pts after double-valve or complex surgery. In multivariable regression, age, diuretic use, cardiopulmonary bypass time and surgery other than isolated CABG were independent predictors of PPM implantation. After 5.6±4.2 years of follow-up, 40% of the pts were PPM dependent. Another 30% of the pts were paced >80% of the time but not PPM dependent. Over 7.2±5 years of follow-up, 2270 (36%) patients died. Patients who had PPM had a higher mortality than those without PPM (45% vs. 36% p=0.02). However, after adjusting for age, sex, type of surgery and cardiopulmonary bypass time, undergoing PPM implantation was no longer associated with long-term mortality (hazard ratio 1.3; 95% confidence interval 0.9 to 1.9; p=0.17).   Conclusions:  In long-term follow-up 30% of the pts who underwent PPM implantation after cardiac surgery were neither PPM dependent and nor paced a substantial amount of time. Requiring PPM implantation after cardiac surgery did not influence long-term survival.
Abstract 17958: Significant Decrease in Ascending Aortic Strain Detected by Speckle-Tracking Algorithms in Patients with Bicuspid Aortic Valve
Authors: Shanna R Sprinkle, Melissa M Levack, Jennifer Chao, Martin G Keane, Martin St. John Sutton, Joseph H Gorman, Robert C Gorman, Benjamin M Jackson
Journal: Circulation (2012)

Purpose: Age-related decreases in circumferential ascending aortic strain can be quantified by applying two-dimensional (2D) speckle-tracking echocardiography algorithms. Applying this technique to...
Forgive and Remember: Managing Medical Failure
Authors: J. G. Anderson
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
The new automated daily mortality surveillance system in Portugal
Authors: P J Nogueira, A Machado, E Rodrigues, B Nunes, L Sousa, M Jacinto, A Ferreira, J  M Falcão, P Ferrinho
Journal: Eurosurveillance (2010)

The experience reported in an earlier Eurosurveillance issue on a fast method to evaluate the impact of the 2003 heatwave on mortality in Portugal, generated a daily mortality surveillance system (VDM) that has been operating ever since jointly with the Portuguese Heat Health Watch Warning System. This work describes the VDM system and how it evolved to become an automated system operating year-round, and shows briefly its potential using mortality data from January 2006 to June 2009 collected by the system itself. The new system has important advantages such as: rapid information acquisition, completeness (the entire population is included), lightness (very little information is exchanged, date of death, age, sex, place of death registration). It allows rapid detection of impacts (within five days) and allows a quick preliminary quantification of impacts that usually took several years to be done. These characteristics make this system a powerful tool for public health action. The VDM system also represents an example of inter-institutional cooperation, bringing together organisations from two different ministries, Health and Justice, aiming at improving knowledge about the mortality in the population.
Abstract 17787: The Majority of Underlying Causes of PEA and Asystole Sudden Deaths Are Non-Cardiac by Systematic Autopsy Investigation
Authors: Zian H Tseng, Lauren McGuire, Benjamin Colburn, Clement Yeh, Philip C Ursell, Anthony S Kim, Jeffrey Olgin, Amy Hart, Ellen Moffatt
Journal: Circulation (2013)

Background: The incidence of ventricular tachycardia/fibrillation (VT/VF) as the presenting rhythm in witnessed sudden cardiac deaths (SCDs) has been declining, with increasing incidence of pulsele...
Abstract 14829: Effect of n-3PUFA on Heart Rate Variability. Data from the GISSI-HF Holter Substudy
Authors: Maria T La Rovere, Simona Barlera, Lidia Staszewsky, Alessandro Mezzani, Paolo Midi, Roberto Marchioli, Aldo Maggioni, Gianni Tognoni, Luigi Tavazzi, Roberto Latini
Journal: Circulation (2011)

BACKGROUND: n-3PUFA supplementation in the GISSI-HF study reduced total mortality in pts with chronic heart failure (CHF) but the mechanism of action is still an open question. One of the study hyp...
Abstract 1702: Multimodality Imaging reveals Tgf{beta} Regulated Increase in MMP Protease Activity at Aneurysmal Lesions in Live Fibulin-4 Mice
Authors: Eric Kaijzel, Piotr Wielopolski, Gerben Koning, Clemens Lowik W Lowik, Monique Bernsen Bernsen, Jeroen Essers
Journal: Circulation (2008)

Fibulins are a six-member protein family hypothesized to function as intermolecular bridges that stabilize the organization of extracellular matrix structures as elastic fibers and basement membran...
Abstract P117: Episodes of Anger are Associated with a Higher Risk of Myocardial Infarction and Acute Coronary Syndrome: Systematic Review and Meta-Analysis
Authors: Elizabeth Mostofsky, Elizabeth A Penner, Murray A Mittleman
Journal: Circulation (2013)

Introduction: Short-term psychological stress is associated with an immediate physiologic response. We assessed the hypothesis that brief episodes of anger may trigger the onset of acute myocardial infarction (MI) and other acute coronary syndromes (ACS). Methods: We performed a literature search of the CINAHL, Embase, PubMed and PsycInfo databases from January 1966 through June 2012 using the key words “anger”, “hostility”, “myocardial infarction” and “acute coronary syndrome” without restrictions. We also reviewed the reference lists of retrieved articles and spoke with authors of relevant work to identify unpublished data. We used an inverse-variance-weighted random effects model to perform a meta-analysis of all epidemiological studies that reported relative risks and 95% confidence intervals (CI) for the association between outbursts of anger and nonfatal MI or ACS. Results: The meta-analysis included four independent case-crossover studies of anger and risk of MI or ACS published between 1995 and 2007 and one unpublished report. Combined, there were 4546 MI cases (two studies) and 462 ACS cases (two studies), including 180 that experienced an episode of anger in the two hours prior to disease onset; two studies were restricted to first MI or ACS and two included first and recurrent events. All studies used the Onset Anger Scale to assess anger episodes, but the studies differed in the cutoff used to define exposure. The association between outbursts of anger and disease risk in the following two hours was 3.46 (95%CI 2.08-5.76; p&lt;0.001). The results were similar for studies of first and recurrent events and were similar for studies of MI and ACS. Conclusions: There is a higher risk of MI and ACS shortly after outbursts of anger. Some of the between-study heterogeneity may be due to regional differences in the type of anger expression and the interpretation of the questions. Further research is necessary to evaluate whether the risk is lower among people who are regularly active.
Abstract 3594: Development of a TRPV1 inducible expression model in MCF-7 breast cancer cells and its potential role in the evaluation of calcium channels as viable therapeutic targets in cancer
Authors: Tina Wu, Jodie Robinson, Gregory R. Monteith, Sarah J. Roberts-Thomson
Journal: Cancer Research (2010)

Abstract Calcium is an important intracellular messenger that regulates many physiological functions such as cellular differentiation, proliferation and apoptosis. Abnormal functioning of calcium signaling pathways may occur during tumorigenesis. Calcium signals are tightly controlled by calcium influx channels and many calcium channels, including those of the transient receptor potential (TRP) ion channel family have altered expression levels in specific cancer types, such as the upregulation of TRPM8 in some prostate cancers. Plasma membrane calcium channels belong to a protein class that can be effectively pharmacologically modulated. Pharmacological agents are available that modify specific TRP calcium channels and some voltage gated calcium channels, such as the inhibition of L-type calcium channels by the anti-hypertensive nifedipine. Both activators and inhibitors of calcium channels overexpressed in cancer cells are potential anti-cancer drugs. This is due to the duality of the calcium signal, whereby calcium can be both a promoter of proliferation but also an inducer of apoptosis. Therefore, calcium channels with increased expression and/or activity in cancer could potentially serve as anti-cancer therapeutic targets. To test this and to explore some of the likely issues related to calcium channels as drug targets in cancer, we have generated a Tet-Off inducible model system where the transient receptor potential vanilloid 1 (TRPV1) calcium channel is over-expressed in the MCF-7 Tet-Off breast cancer cell line. TRPV1 has been chosen in this model, due to the wide availability of selective inhibitors and activators to this channel. TRPV1 functional activity in the model system was measured by calcium influx using the Fluorescent Imaging Plate Reader (FLIPR) and the calcium sensitive probe Fluo-4. Capsaicin, a TRPV1 agonist had an EC50 of 2 × 10-7 M for increased cytosolic free calcium in the absence of doxycycline and an EC50 of 1 × 10-6 M in the presence of doxycycline (1µg/ml). In this same stable cell line, peak cytosolic responses were significantly higher in the absence of doxycycline compared to the presence of doxycycline. This suggests a tight regulation of TRPV1 expression in the Tet-Off system. Future studies will characterize the consequences of TRPV1 over-expression and TRPV1 pharmacological modulators on cellular proliferation and apoptosis pathways. This model system could be an important tool to address the feasibility of calcium channels as drug targets in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3594.
Soundings: Magnificus in distress
Authors: George Dunea
Journal: BMJ (2000)

When Professor Magnificus does ward rounds followed by his extensive retinue, everybody admires his exquisite bedside manner. If he detects a murmur that nobody has heard, or feels a spleen that nobody has felt, the students think that he is the very incarnation of Sir William Osler. Brilliant are the comments that he makes after each case presentation, as he draws from his extensive clinical experience and brings in relevant or irrelevant facts from his bench research. Indeed, he represents the incarnate role model of the compleat physician.

Of late, however, clouds have been blackening the professor's horizon. At the university many of his research grants have been approved but not funded. Moneys for faculty salaries must increasingly come from clinical activities, just as managed care organisations are signing up the university's patients. He now spends endless hours in meetings on recruiting patients; on referral networks; provider satisfaction; managed care contracts; clinical guidelines; and quality assurance. New standards of note taking have been promulgated: bureaucrats and malpractice lawyers say that what is not documented is considered not to have been done. Several hospitals have been sold or merged; and there is constant talk of consolidations, downsizing, rationalisation, and “developing synergies.”

The professor is also swamped with paper work to satisfy numerous accrediting and review bodies. He spends much time credentialling, being required to regularly review the perfomance and qualifications of dozens of doctors and even nurse practitioners. He is expected to comment on their ethics; cooperation with other providers; attitude towards patients; compliance with educational requirements; attendance at meetings; malpractice claims; and reports from quality assurance and medical records committees. He has been assigned to several task forces; has a book to review; a manuscript to complete; and still tries to keep things going in the laboratory. He has frequent meetings with the dean, who expects more grants, more research papers. At night he is too wound up to sleep, but wonders what new problems the morning will bring. He thinks of the old days when there were no provider networks, no managed care contracts, when grants were plenty, when research fellows flocked to his unit, and he had plenty of money to pay them.
Abstract 402: Endothelial Specific Jagged-1/Notch Signal in Bone Marrow Niche Regulates Endothelial Progenitor Cell Development
Authors: Sang Mo Kwon, Naruske Kamei, Ayumi Yokoyama, Miki Horii, Haruchika Masuda, Takayuki Asahara
Journal: Circulation (2008)

The developmental cascade of endothelial progenitor cells (EPCs) in response to environmental signals is dynamically regulated by tight-communication between stem cells and stromal cells in bone marrow niches. We have recently reported that Jagged-1 dependent signals specifically regulated EPC-mediated vascularization using mice of Mx-cre dependent inactivation of jagged-1. However, the specific contribution of EPC development via modulating endothelial Jagged-1/Notch axis remain unclear. EPC colony forming capacity of CD34(−)/c-kit(+)/Sca-1(+)/Lin(−) stem cells in tamoxifen-treated Tie2cre-Jagged-1 null mice are drastically enhanced, although the CFU-EPC in CD34(+)/c-kit(+)/Sca-1(+)/Lin(−) progenitor cells was significantly impaired in Jagged-1 null mice. Moreover, the impaired EPC development was also confirmed in single cell-derived EPC colony forming assay. Notably, the development of primitive EPC, an early stage of EPC development, was significantly increased in stem cells, while progenitors derived from BM niche did not give rise to form definitive EPC, a late stage of EPC development. Similarly, we observed markedly decreased cell number and CFU-EPC of progenitor subset (Sca-1+/c-Kit+) in cultured EPCs. Isolated Jag-1 deficient progenitors in cultured EPCs never gave rise to definitive EPC, while WT-derived progenitor did. When co-culture with stromal cells derived from endothelial specific Jagged-1 null mice, stem cells could not develop functional EPCs. EPCs from endothelial specific Jagged-1 deficient niche showed impaired in vitro migration capacity in response to VEGF, SDF-1a, SCF or TPO, as well as the decreased incorporation ability into ischemic neo-vessel. In hind limb ischemia models, we observed the significantly reduced blood vessel regeneration with the decreased capillary density in endothelial specific Jagged-1 null mice. In conclusion, the present report clearly showed for the first time that the Jagged-1/Notch axis plays a pivotal role in EPC development in special niche, suggesting that modulation of EPC development via regulating Jagged-1/Notch axis provide a clue of therapeutic tissue regeneration.