tbuckley/cabot-search huggingface dataset:
Abstract 5102: Sex Hormones and the Risk of Coronary Artery Calcium Progression in the Multi-Ethnic Study of Atherosclerosis
Authors: Erin D Michos, Dhananjay Vaidya, Susan R Heckbert, Mary Cushman, Sherita H Golden, Pamela Ouyang
Journal: Circulation (2008)

Background:  The association of sex hormones (SH) with subclinical atherosclerosis is controversial. Hormone replacement therapy (HRT) is associated with less coronary artery calcium (CAC) progression in some studies. HRT also raises estradiol (E2) levels. We evaluated the association of endogenous SH levels including E2 with CAC progression during followup in 1647 postmenopausal women not on HRT and 2698 men the Multi-Ethnic Study of Atherosclerosis (MESA).   Methods:  CAC was quantified by computed tomography, and Testosterone (T), E2, dehydroepiandrosterone (DHEA), and SH binding globulin (SHBG) were measured at baseline. Followup CAC was measured in half the cohort (randomly selected) at the second exam and the other half at third exam, after an average of 1.6 and 3.2 years, respectively. We used relative risk regression to determine the risk of developing prevalent CAC(>0 Agatston units) at followup for those without CAC at baseline and robust linear regression to study change in CAC score for those with prevalent baseline CAC. Models were adjusted for age, ethnicity, BMI, systolic and diastolic blood pressure (BP), diabetes, total cholesterol, HDL-c, use of BP and cholesterol meds, smoking, alcohol, followup time, and other SH. Models were performed separately by sex.   Results:  See table. Among those without baseline CAC, only greater E2 in women was nearly associated with increased risk of developing CAC at followup. Among those with prevalent baseline CAC, greater T was associated with less CAC at followup in both men and women; while greater DHEA in women and greater SHBG in men were associated with increases in CAC.   Conclusion:  In women without baseline CAC, higher E2 levels may be nearly associated with increased risk of developing CAC. In those with prevalent CAC, higher T levels may be protective against progression in both sexes while higher DHEA (in women) and SHBG (in men) may worsen progression.
Abstract 1492: Epigenetic Control of the eNOS Promoter by DNA Methylation in Vasculogenic Progenitor Cell Populations
Authors: Georgios J Vlachojannis, Carmen Urbich, Andreas M Zeiher, Stefanie Dimmeler
Journal: Circulation (2007)

DNA methylation has been shown to play an essential role in both the transcriptional regulation and endothelial cell-specific expression of the human endothelial nitric oxide synthase (eNOS) gene. Further, recent data emphasizes an important role of eNOS in stem cell biology in particular with regard to progenitor cell mobilization and vasculoprotective properties. We assessed the hypothesis that stem and vasculogenic progenitor cells will exhibit different DNA methylation patterns of the eNOS promoter region dependent on their vascular fate. Endothelial progenitor cells (EPCs), mesangioblasts, CD34+, HUVECs and microvascular endothelial cells (MVECs) were cultivated and genomic DNA was subjected to sodium bisulfite treatment. The final PCR products were subcloned and sequenced (5–10 clones). Whereas the eNOS proximal promoter was either devoid or very lightly methylated in the human endothelial cell types including HUVECs and MVECs, the promoter was heavily methylated in the examined progenitor and stem cell types namely CD34+ and mesangioblasts. Surprisingly, EPCs also exhibit a profound methylation of the eNOS promoter (see Figure ). In conclusion, we have demonstrated that progenitor and stem cells including EPCs, CD34+ and mesangioblasts - although committed to a vascular fate - are in contrast to endothelial cell types heavily methylated in the promoter region of the eNOS gene suggesting epigenetic silencing at this level of maturation. The functional importance of this finding in particular regarding vasculoprotective potency and the modulation of methylation during progenitor cell maturation is subject of future studies. Methylation pattern of the eNOS promoter
Abstract 18427: 27-Hydroxycholesterol, the First Identified endogenous SERM, Promotes Atherogenesis in Mice
Authors: Michihisa Umetani, David J Mangelsdorf, Philip W Shaul
Journal: Circulation (2010)

Estrogen has important impact on cardiovascular health, and in mice estrogen actions mediated by estrogen receptor (ER) α prevent atherosclerosis and promote reendothelialization. Previously we dis...
Analysis of the PAX6-Mediated Suppression Pathways in Gliomas: Downregulation of MMP2 Expression
Authors: Debra A. Mayes, Xiaosong Wu, Yue Teng, Longjian Liu, Yi-Hong Zhou
Journal: Cancer Research (2005)

2809  Glioblastoma multiform (GBM) is the most common and most malignant primary brain tumor. We have reported that the expression of PAX6 is decreased in most GBM patient samples when compared to adjacent normal tissue and anaplastic astrocytomas (AAs). Lower PAX6 expression in tumor tissue is an indication of an unfavorable prognosis for patients with malignant astrocytic gliomas (Zhou et. al. Clin. Can. Res. 9:3369-75). PAX6 encodes a transcription factor critical in the development of the eye and central nervous system. In contrast to the decreased expression of PAX6 in GBMs, we observed an increase in the expression of PAX6 in the GBM cell line U251 after introducing a normal chromosome 10. Loss of heterozygosity (LOH) of chromosome 10 occurs in up to 80% of human GBM cases. Therefore, the reduced expression of PAX6 in GBMs may result from the loss of unidentified tumor suppression gene(s) in chromosome 10; however, this is not a simple side effect of LOH of chromosome 10. Overexpression of PAX6 via stable transfection of a PAX6/pRC-CMV construct in the GBM cell line U251HF suppressed anchorage-independent growth in vivo and tumor formation in vitro. This data is consistent with the hypothesis that PAX6 may have a tumor-suppressor function in GBM (Zhou et. al. J. Neuro-Oncology, in print). Microarray hybridization using Affymetrix chips revealed alterations of matrix metalloproteinase-2 (MMP2) gene expression in the suppressed U251HF PAX6-transfected cells. This data was confirmed by real-time quantitative reverse transcription PCR from cells grown in vitro and in the brain of nude mice. Moreover, there is a reverse correlation between the expression of PAX6 and MMP2 in GBMs, but not in AAs. MMP2 is a well-known protease involved in cell invasion and the malignant progression of gliomas. MMP2 was also shown to be suppressed at a functional level in gelatin zymography assays in PAX6 transfectant cells. This suppression correlates with the near abolition of the ability of all PAX6 transfectants to invade in matrigel invasion assays; however, cells expressing a dominant negative mutant form of PAX6 (PAX6-344) displayed a significant enhancement in their ability to invade in this assay. Luciferase MMP2 promoter assays have indicated that the lower expression level of MMP2 in PAX6-transfected cells is due to lower MMP2 promoter activity. In conclusion, our data indicate that PAX6 plays an important role in suppressing the formation of GBM by suppressing the expression of MMP2. Identification and functional characterization of the cis-element responsible for the suppression of the MMP2 promoter activity by PAX6 is being examined.
Abstract 3702: Anemia as an Independent Predictor of Perioperative and Long Term Cardiovascular Outcome in Patients Scheduled for Elective Vascular Surgery
Authors: Martin Dunkelgrun, Sanne Hoeks, Dustin Goei, Gijs Welten, Radosav Vidakovic, Yvette van Gestel, Olaf Schouten, Ron van Domburg, Don Poldermans
Journal: Circulation (2007)

BACKGROUND: Anemia has been shown to be an independent risk factor for adverse cardiac outcome in various populations. This study evaluated the predictive value of anemia in patients scheduled for elective vascular surgery. METHODS: In total, 1211 patients (76% male, age 68 ± 11 yrs) were enrolled. Anemia was defined as serum hemoglobin &lt; 13 g/dL for men and &lt; 12 g/dL for women, as defined by WHO. Anemia was divided into tertiles to compare mild, moderate and severe anemia with non-anemic patients. Outcome measures were 30-day and 5-year cardiac events (CE) (cardiac death or myocardial infarction). Mean follow up was 3.4 ± 3.2 years. Multivariable linear and Cox regression analysis was used, adjusting for age, sex, type of surgery and baseline characteristics, including angina, myocardial infarction, heart failure, diabetes and renal failure. Data are presented as HRs, with 95% confidence intervals. RESULTS: In total, 74 (6%) patients experienced a 30-day CE and 199 (16%) a 5-year CE. Anemia was present in 399 (33%) patients, of which 133 were mild, 133 moderate, and 133 severe anemia. The presence of anemia was associated with renal failure, diabetes and heart failure. CE free survival at 30 days and 5 years was worse for patients with anemia (Figure ). After adjustment for all clinical risk factors, the 30-day HRs for a CE per anemia group were; mild 1.8, 1.0 – 4.1, moderate 2.9, 1.4 – 6.2, and severe 7.6, 4.1–13.1, and 5-year HRs for CE per anemia group were; mild 2.2, 1.3–3.8, moderate 3.6, 2.4 –5.6, and severe 6.6, 4.6 –9.6. CONCLUSION: The presence and severity of preoperative anemia are significant predictors of 30-day and 5-year cardiac events in patients undergoing elective vascular surgery.
Abstract 2474: Rho-Kinase Inhibition Improves Endothelium-Dependent Vasodilation during Hyperinsulinemia in Patients with Metabolic Syndrome
Authors: Francesca Schinzari, Manfredi Tesauro, Valentina Rovella, Augusto Veneziani, Nadia Mores, Domenico Melina, Carmine Cardillo
Journal: Circulation (2008)

Impaired insulin-mediated vasodilation in the skeletal muscle may be involved in the development of hypertension in patients with metabolic syndrome (MetS) and contribute to insulin resistance by diminishing the glucose uptake. Rho-kinase, an effector of the small G protein Rho A, plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of insulin receptor substrate-1 in blood vessels. We therefore examined the role of Rho-kinase in the pathophysiology of impaired vascular reactivity in patients with MetS by evaluating the effect of Rho-kinase inhibition on NO-dependent vasodilation during hyperinsulinemia. Forearm blood flow (FBF) responses to acetylcholine (ACh), a stimulus for endothelial release of NO, and sodium nitroprusside (SNP), an exogenous NO donor, were assessed during insulin administration (0.1 mU/Kg/min) using the forearm perfusion technique in patients with MetS (n=10) and matched controls (n=10). Patients with MetS were then randomized to intra-arterial infusion of either fasudil (inhibitor of Rho-kinase, 200 μg/min) or placebo and reactivity to ACh and SNP was reassessed. During hyperinsulinemia, vasodilator responses to both ACh and SNP were blunted in patients with MetS (both P&gt;0.001 vs. controls). In patients who received fasudil, its administration did not change unstimulated FBF (P=0.75 vs. insulin alone); the vasodilator response to ACh, however, was significantly enhanced by fasudil (P=0.009 vs. insulin alone), while the response to SNP was not significantly changed (P=0.56). In patients with MetS who received placebo, vascular reactivity to both ACh and SNP was not different than before (both P&gt;0.05). In conclusion, Rho-kinase inhibition during hyperinsulinemia improves endothelium-dependent vasodilator responsiveness in patients with MetS. This suggests that, under those conditions, intravascular activation of Rho-kinase is involved in the pathophysiology of endothelial dysfunction and may constitute a critical mediator linking metabolic and hemodynamic abnormalities in insulin resistance. As a consequence, targeting Rho-kinase might beneficially impact both vascular function and insulin sensitivity in patients with MetS.
Ibrutinib (PCI-32765) Antagonizes Rituximab-Dependent NK-Cell Mediated Cytotoxicity
Authors: Holbrook E Kohrt, Idit Sagiv-Barfi, Sarwish Rafiq, Sarah E.M. Herman, Jonathan P Butchar, Carolyn Cheney, Xiaoli Zhang, Joseph J. Buggy, Natarajan Muthusamy, Ronald Levy, Amy J Johnson, John C. Byrd
Journal: Blood (2013)
HENRI DE MONDEVILLE.
Authors: C C Clarke
Journal: JAMA (1895)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 1375: Brain Renin Angiotensin Blockade Attenuates Cytokines and Oxidative Stress in the Paraventricular Nucleus of Hypothalamus and Decreases Sympathoexcitation in Heart Failure Rats
Authors: Ying Ma, Yu-Ming Kang*, Zhi-Ming Yang, Joseph Francis*
Journal: Circulation (2007)

Introduction: Neurohumoral mechanisms play an important role in the pathophysiology of congestive heart failure (HF). Recent studies suggest that the brain renin angiotensin system (RAS) plays an important role in regulating body fluids and sympathetic drive in HF. In addition, it has been shown that there is cross talk between cytokines and RAS in cardiovascular disease. In this study we determined whether blockade of brain RAS attenuate inflammatory cytokines and oxidative stress in HF rats. Methods and Results: Adult male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation to induce HF and confirmed by echocardiography. Rats were treated with an angiotensin type 1 receptors (AT1-R) antagonist losartan (LOS, 20 μg/hr, ICV) or vehicle (VEH) for 4 weeks. At the end of the study, left ventricular (LV) function was measured by echocardiography and rats were sacrificed, and brain and plasma samples were collected for measurements of cytokines and superoxide using immunohistochemistry, Western blot and real time RT-PCR. HF rats induced significant increases in Nuclear Factor-kappaB (NF-κB) p50-positive neurons and activated microglia in the paraventricular nucleus (PVN) of hypothalamus, and TNF-α, IL-1β, IL-6 and NF-κB p50 in hypothalamus when compared with sham rats. These animals also had increased staining for dihydroethidium (DHE) and plasma levels of norepinephrine (NE), an indirect indicator of sympathetic activity. In contrast, ICV treatment with LOS attenuated cytokine expression and oxidative stress in the PVN and hypothalamus when compared with VEH treated HF rats. ICV treatment with LOS also reduced plasma NE levels, and proinflammatory cytokine, heart weight to body weight ratio with decreased LV end-diastolic pressure. Conclusions : These findings suggest the cross talk between the cytokines and renin angiotensin system within the brain contribute to sympatho-excitation in HF.
Ventilatory assessment of asthmatic patients incremental shuttle walk test: A pilot study
Authors: Ivana G. Labadessa, Audrey Borghi e Silva, Adriana S.G. de Araujo, Soraya Pilon Jürgensen, Cristiane L. Garbim, Valéria A. Pires Di Lorenzo
Journal: European Respiratory Journal (2014)

Background:  Exercise intolerance in asthmatics occurs by reduced ventilatory capacity and dyspnea as well as the occurrence of exercise-induced bronchoconstriction (EIB).  Aims:  1) assess ventilatory responses at the peak of the Incremental Shuttle Walk Test (ISWT) and constant cardiopulmonary exercise test (CCPET); 2) determine the presence of EIB in patients with asthma ISWT.  Methods  :  20 asthmatic (28±8 years; FEV1 98±20% predictive, FEV1/FVC 75±20%) were evaluated. In two non-consecutive days, a CCPET test on a treadmillwith intensity at 40% of ventilatory demand (VE/MVV) in incremental CPET and an ISWT test with ventilation uptake (VE) (Oxycon) and VE/VCO 2  were performed. Three maneuvers of FVC were performed before the tests and at the end, a FVC maneuver every 5 minutes until 30 minutes of recovery (fall of FEV1≥ 10%, BIE was considered).  Results:  In ISWT, distance traveled was 540±83 meters, reaching 73±8% pred. In CCPET, the peak speed reached was 5.6±1.4 km / h, the slope of 8.5±4% and the time of 10±1 minute test. The values for peak ISWT and CCPET respectively were: VE/VCO 2  = 32±8 vs. 29±7, no significant difference was found and in the VE/MVV= 0.5±0.2 vs. 0.4±0.2 significant difference was found (p=0,032). Out of 20 asthmatic patients, 15 presented in BIE ISWT (Δ=-17±4) and CCPET (Δ=-12±2%).  Conclusion : The ventilatory efficiency was similar in both tests and ventilatory demand was higher in ISWT. The ISWT can be a tool to assess the presence of EIB in this specific population.   Financial support: no2011/23771-7   Sao Paulo Research Foundation (FAPESP) .
Abstract 562: Adeno-Associated Virus-Mediated Gene Transfer and Activation of Insulin-like Growth Factor-I Increases Cardiac Function in Chronic Severe Heart Failure
Authors: Toshiyuki Takahashi, N. Chin Lai, Mei Hua Gao, Tong Tang, David M Roth, Atsushi Miyanohara, H. Kirk Hammond
Journal: Circulation (2006)

Background: Insulin-like growth factor-I (IGF-I) has pleiotropic effects, including positive inotropic, anti-apoptotic, angiogenic and pro-myogenic in the heart. We constructed a serotype 5 adeno-associated virus vector encoding IGF-I under tet-regulation (AAV5.IGFI-tet) to assess the effects of exogenous IGF-I expression on cardiac function in chronic severe heart failure induced by myocardial infarction (MI). We tested the hypothesis that increased cardiac expression of IGF-I would increase the function of the failing heart. Methods and Results: Twenty-one 3-month old mice underwent indirect intracoronary delivery of AAV5.IGFI-tet (5x10 11 vp), followed immediately by permanent left coronary artery occlusion. Five weeks later, the 10 mice that survived MI and met entry criteria (LVEF&lt;40% and LV end-diastolic diameter&gt;4.5 mm; echocardiography), randomly were assigned to receive doxycycline in their water supply, which activates cardiac IGF-I expression (IGF-On, n=5) or receive regular water (i.e., no treatment, IGF-Off, n=5). After 5 wk of treatment (10 wk from MI), echocardiography showed that IGF-On mice had increased LVEF while the IGF-Off mice showed continued decline (ΔLVEF, IGF-On: +2.3 ± 2.1%; IGF-Off: −5.6 ± 1.9%, n=5 for each group, p=0.03), and pressure-volume analyses showed increased cardiac output (IGF-On: 6.7 ± 1.1 ml/min; IGF-Off: 4.0 ± 0.3 ml/min, n=3 for each group, p=0.08) and stroke volume (IGF-On: 17 ± 3 μl; IGF-Off: 9 ± 1 μl, n=3 for each group, p=0.05). Rates of apoptosis, assessed by TUNEL staining, were reduced in viable LV (Border zone, IGF-On: 125 ± 5 /10 5 nuclei, n=3; IGF-Off: 416 ± 40 /10 5 nuclei, n=4, p&lt;0.02; Remote zone, IGF-On: 85 ± 7 /10 5 nuclei, n=3; IGF-Off: 207 ± 28 /10 5 nuclei, n=4, p&lt;0.01). Conclusion: Increased cardiac expression of IGF-I improves LV function and reduces apoptosis in the failing heart. These data suggest a new potential treatment strategy for severe heart failure.
Severe daytime somnolence in patients treated with an MAOI
Authors: M H Teicher, B M Cohen, R J Baldessarini, J O Cole
Journal: American Journal of Psychiatry (1988)

Eight patients with hypersomnolent, anergic major depression benefited markedly from treatment with relatively high doses of phenelzine or tranylcypromine but experienced intense afternoon somnolence and disrupted sleep. Reducing the dose of monoamine oxidase inhibitor (MAOI) or substituting isocarboxazid sometimes provided relief, but altering the schedule of drugs or meals did not. Bedtime sedation alleviated the disrupted sleep but had little effect on daytime somnolence. The mechanism underlying this side effect is unknown; sleep deprivation, narcolepsy, or hypotension does not account for it. Patients given an MAOI should be assessed for this disturbance and cautioned to avoid risk of injury when it occurs.
Early cardiovascular disease markers in “healthy” OSA patients are correlated with sympathetic activity
Authors: Donato Lacedonia, Renaud Tamisier, Jean-Philippe Baguet, Jean-Louis Pepin, Patrick Levy
Journal: European Respiratory Journal (2011)

Rationale: Obstructive sleep apnea syndrome (OSAS) is associated with high Sympathetic activity (SA) and a subsequent risk of hypertension and atherosclerosis. Objectives were to assess SA and its impact on early cardiovascular disease markers.

Methods: In 25 otherwise healthy OSA and 13 aged-matched controls we measured SA by direct peroneal microneurography: Muscle Sympathetic Nerve Activity (MSNA). All subjects underwent a full polysomnography, 24h Ambulatory Blood Pressure Monitoring (ABPM), arterial stiffness by Pulse Wave Velocity (PWV), vascular reactivity by Peripheral Arterial Tone (PAT) and early atherosclerosis by arterial carotid Intima Media Thickness (IMT). Preliminary data in 7 OSA and 7 controls were obtained after 6 month (CPAP for OSA).

Results: OSA patients (BMI 25.9±2.8 kg/m2; AHI 38.8±20.4/h; Age 53±11 yrs) and healthy controls (BMI 23.9±2.6 kg/m2; AHI 7.9±5.8/h; Age 48±13 yrs). They were comparable for all but for BMI (p<0.05). At baseline SA was higher in OSA than in controls 39.8±9.4 vs 30.6±7.3 bursts/min p<0.01). SA was correlated with OSAS severity (mean nocturnal SaO2, -0.401 p<0.05). SA also correlated with cardiovascular markers, vascular reactivity PAT (-0.354 p<0.05), systolic and diastolic office (0.406 p<0.05 and 0.536 p<0.001) and ABPM blood pressure (0.4 p<0.05 and 0.514 p<0.01), and IMT (0.464 p<0.01). 6-month CPAP treatment induced a significant reduction in SA -10.3±8.1 vs 1.5±5.9, bursts/min p<0.01).

Conclusion: Early cardiovascular disease markers are correlated with SA, supporting the fact that SA is likely to play a significant role in the cardiovascular morbidity of OSA patients.
THE ARCHIVES OF INTERNAL MEDICINE.
Authors: 芳郎 上塚
Journal: JAMA (2007)

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