tbuckley/cabot-search huggingface dataset:
ST-Segment Elevation in Conditions Other Than Acute Myocardial Infarction
Authors: Kyuhyun Wang, Richard W. Asinger, Henry J.L. Marriott
Journal: New England Journal of Medicine (2003)

Many conditions other than acute myocardial infarction cause elevation of ST segments on an electrocardiogram. This review explains the conditions that may mimic acute myocardial infarction electrocardiographically. Because decisions about reperfusion therapy must be made quickly for patients with myocardial infarction, it is important to recognize and differentiate other causes of ST-segment elevation.
Incidence and Predictors of Myocardial Infarction after Kidney Transplantation
Authors: Krista L. Lentine, Daniel C. Brennan, Mark A. Schnitzler
Journal: Journal of the American Society of Nephrology (2004)

The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000). Extended Cox’s hazards analysis was used to identify independent clinical correlates of PTMI (hazard ratio [HR]) and to examine PTMI as an outcomes predictor. Among 35,847 eligible participants, the cumulative incidence of PTMI was 4.3% (95% confidence interval [CI], 4.1 to 4.5%), 5.6% (95% CI, 5.3 to 5.8%), and 11.1% (95% CI, 10.7 to 11.5%) at 6, 12, and 36 mo, respectively. Risk factors for PTMI included older recipient age, pretransplantation comorbidities (diabetes, angina, peripheral vascular disease, and MI), transplantation from older donors and deceased donors, and delayed graft function. Women, blacks, Hispanics, and employed recipients experienced reduced risk. The hazard of PTMI rose after a diagnosis of posttransplantation diabetes (HR, 1.60; 95% CI, 1.35 to 1.88) and markedly increased after graft failure (HR, 2.78; 95% CI, 2.41 to 3.19). In separate analyses, PTMI predicted death-censored graft failure (HR, 1.89; 95% CI, 1.63 to 2.20) and strongly predicted death in a manner that declined with time after PTMI. Risk factors for PTMI include potentially modifiable posttransplantation complications. Because PTMI in turn predicts graft failure and death, reducing the risk for PTMI may improve outcomes after kidney transplantation.
Response to: ‘Does adding the presence of MRI detected bone marrow oedema improve the accuracy of the 2010 EULAR/ACR criteria for rheumatoid arthritis?’ by Nieuwenhuis<i>et al</i>
Authors: Mami Tamai, Atsushi Kawakami
Journal: Annals of the Rheumatic Diseases (2014)

Response to: 'Does adding the of MRI detected bone marrow oedema improve the accuracy of the 2010 EULAR/ACR criteria for rheumatoid arthritis?' by Nieuwenhuis et alWe are very excited to receive the interesting results from Leiden Early Arthritis Clinic. 1 The major difference between our results 2 and the results from the Leiden Early Arthritis Clinic is the value of MRI-detected bone marrow oedema (BME) to improve the accuracy of the 2010 Rheumatoid Arthritis Classification Criteria.Although both groups have used 1.5 T MRI and obtained the identical definition of BME, we can find the two differences regarding the procedure of MRI and patient population from the Leiden Early Arthritis Clinic.First, we have examined both hands though Nieuwenhuis et al scanned only unilateral hand.Our previous data showed that the sensitivity of detection of BME declined by unilateral hand compared with both hands. 3Our present MRI data are derived from gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI; however, Nieuwenhuis et al might have used plain MRI.If so, the sensitivity of detection of BME also declines by plain MRI compared with Gd-DTPA-enhanced MRI.The above differences of MRI procedure may affect the difference of MRI results of both groups.Second, our patient population is more early (median 8 weeks vs 10.7 weeks) and more anticitrullinated protein antibody (ACPA)-positive (34.1% vs 22%).Therefore, we might examine more active and rheumatoid arthritis (RA)-prone 1987-undifferentiated arthritis (UA) patients compared with the Leiden Early Arthritis Clinic.These clinical characteristics may also result in the difference of the role of MRI BME to assist the diagnostic performance of 2010 Rheumatoid Arthritis Classification Criteria.In conclusion, the difference of role of MRI-detected BME is found between our cohort and the Leiden Early Arthritis Clinic; however, these might be attributable to the differences of MRI procedure and patient characteristics.
Human <b> <i>In vivo</i> </b> Radiation-Induced Biomarkers
Authors: Sally A. Amundson, Marcy B. Grace, Christopher B. McLeland, Michael W. Epperly, Andrew Yeager, Qimin Zhan, Joel S. Greenberger, Albert J. Fornace
Journal: Cancer Research (2004)

Abstract After initially identifying potential biomarkers of radiation exposure through microarray studies of ex vivo irradiated human peripheral white blood cells, we have now measured the in vivo responses of several of these biomarker genes in patients undergoing total body irradiation. Microarray analysis has identified additional in vivo radiation-responsive genes, although the general in vivo patterns of stress-gene induction appear similar to those obtained from ex vivo white blood cell experiments. Additional studies may reveal correlations between responses and either diagnosis or prognosis, and such in vivo validation marks an important step in the development of potentially informative radiation exposure biomarkers.
Down-Regulation of Insulin-Like Growth Factor I Receptor Activity by NVP-AEW541 Has an Antitumor Effect on Neuroblastoma Cells<i>In vitro</i>and<i>In vivo</i>
Authors: Barbara Tanno, Camillo Mancini, Roberta Vitali, Mariateresa Mancuso, Heather P. McDowell, Carlo Dominici, Giuseppe Raschellà
Journal: Clinical Cancer Research (2006)

Signaling through insulin-like growth factor I receptor (IGF-IR) is important for growth and survival of many tumor types. Neuroblastoma is sensitive to IGF.We assessed the ability of NVP-AEW541, a recently developed small molecule that selectively inhibits IGF-IR activity, for neuroblastoma growth effects in vitro and in vivo. Our data showed that, in a panel of 10 neuroblastoma cell lines positive for IGF-IR expression, NVP-AEW541 inhibited in vitro proliferation in a submicromolar/micromolar (0.4-6.8) range of concentrations.As expected, NVP-AEW541 inhibited IGF-II-mediated stimulation of IGF-IR and Akt. In addition to growth inhibition, the drug also induced apoptosis in vitro. Oral administration of NVP-AEW541 (50 mg/kg twice daily) inhibited tumor growth of neuroblastoma xenografts in nude mice. Analysis of tumors from the drug-treated animals revealed a marked apoptotic pattern and a decrease in microvascularization compared with controls. Interestingly, quantitative real-time PCR detected both in vitro and in vivo a significant down-regulation of mRNA for vascular endothelial growth factor (VEGF) caused by NVP-AEW541. In addition, in Matrigel-coated chambers and in severe combined immunodeficient mice tail vein injected with neuroblastoma cells, tumor invasiveness was significantly reduced by this agent. Analysis of IGF-IR expression in a series of 43 neuroblastoma primary tumors revealed IGF-IR positivity in 86% of cases.Taken together, these data indicate that NVP-AEW541 can be considered as a novel promising candidate for treatment of neuroblastoma patients.
β3-Adrenergic regulation of an ion channel in the heart—inhibition of the slow delayed rectifier potassium current IKs in guinea pig ventricular myocytes
Authors: R Bosch
Journal: Cardiovascular Research (2002)

Objectives:IKs, the slow component of the delayed rectifier potassium current, underlies a strong β-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in IKs. Recent work has pointed to an opposing biological effect of β1- and β3-adrenoceptors in the heart. However the role of these subtypes in the regulation of cardiac ion channel function is unknown. Methods: We investigated the effects of β1- and β3-adrenoceptor modulation on IKs in guinea-pig ventricular myocytes, using patch-clamp techniques. Results: Superfusion with 100 nmol/l isoproterenol increased the step current amplitude by 81.3±8.0%. In contrast, after block of β1- (1 μmol/l atenolol) and β2-receptors (1 μmol/l ICI118,551), isoproterenol induced a reduction of the step current amplitude by 34.3±3.5%. The β3-selective agonist BRL37344 significantly reduced the IKs step current at +70 mV in a concentration-dependent manner (IC50: 5.01 nmol/l). In the presence of bupranolol (β1-, β2- and β3-adrenoceptor antagonist), the effect of BRL37344 was markedly attenuated, from 27.3±5.6% (100 nmol/l BRL37344 alone) to 4.0±1.3% (100 nmol/l BRL37344+1 μmol/l bupranolol). BRL37344 (100 μmol/) did not alter current amplitudes of KvLQT1/minK expressed in CHO cells or in Xenopus oocytes, excluding a direct effect of BRL37344 on the channel. 1 μmol/l BRL37344 mildly prolonged action potentials in guinea pig ventricle (APD90:+7.8%) Conclusions: We have demonstrated a functional coupling between the β3-adrenoceptor and ion channel function in the mammalian heart. Our findings point to a potential role for β3-adrenoceptors in cardiac electrophysiology and pathophysiology.
Production-comprehension asymmetries
Authors: Fernanda Ferreira
Journal: Behavioral and Brain Sciences (2004)

Pickering &amp; Garrod's (P&amp;G's) mechanistic theory of dialogue is a major advance for psycholinguistics. But the commitment to representational parity in production and comprehension is problematic. Recent research suggests that speakers frequently produce a structure that listeners find ungrammatical and have trouble understanding. If the grammars of the two systems are different, then the assumption of representational parity must be relaxed.
Estrogen Replacement Therapy and Ovarian Cancer Mortality in a Large Prospective Study of US Women
Authors: Carmen Rodriguez
Journal: JAMA (2001)

Context Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers.The effect of postmenopausal estrogen use on ovarian cancer is not established. ObjectivesTo examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. Design and SettingThe American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996.Participants A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. Main Outcome MeasureOvarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT).Results A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up.Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96).Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37).Duration of use was associated with increased risk in both baseline and former users.Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17),while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25).Annual age-adjusted ovarian cancer death rates per 100000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users.Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use Ͻ15 years ago, 2.05; 95% CI, 1.29-3.25;RR for last use Ն15 years ago, 1.31; 95% CI, 0.79-2.17). ConclusionsIn this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.
Reversal of glibenclamide-induced coronary vasoconstriction by enhanced perfusion pulsatility: possible role for nitric oxide
Authors: P Pagliaro
Journal: Cardiovascular Research (2000)

Objectives: ATP-sensitive potassium channels (K+ATP) prominently contribute to basal coronary tone; however, flow reserve during exercise remains unchanged despite channel blockade with glibenclamide (GLI). We hypothesized that increasing perfusion pulsatility, as accompanies exercise, offsets vasoconstriction from K+ATP-channel blockade, and that this effect is blunted by nitric oxide synthase (NOS) inhibition. Methods: In 31 anaesthetized dogs the left anterior descending artery was blood-perfused by computer-controlled servo-pump, with real-time arterial perfusion pulse pressure (PP) varied from 40 and 100 mm Hg at a constant mean pressure and cardiac workload. Results: At control PP (40 mm Hg), GLI (50 μg/min/kg, i.c.) lowered mean regional coronary flow from 37±5 to 25±4 ml/min (P<0.001). However, this was not observed at 100 mm Hg PP (41±2 vs. 45±4). NOS inhibition by NG-monomethyl-l-arginine (L-NMMA) did not alter basal flow at 40 mm Hg PP, but modestly lowered flow (−5%, P<0.001) at higher PP (100 mm Hg), reducing PP-flow augmentation by −36%, and acetylcholine (ACh) induced flow elevation by −39%. Co-infusion of L-NMMA with GLI resulted in net vasoconstriction at both PP levels (−60% and −40% at 40 and 100 mm Hg PP, respectively). Unlike GLI, vasoconstriction by vasopressin (−43±3% flow reduction at 40 mm Hg PP) or quinacrine (−23±7%) was not offset at higher pulsatility (−44±4 and −23±6%, respectively). Neither of the latter agents inhibited ACh- or PP-induced flow responses, nor did they modify the effect of L-NMMA on these responses. Conclusions: Increased coronary flow pulsatility offsets vasoconstriction from K+ATP blockade by likely enhancing NO release. This mechanism may assist exercise-mediated dilation in settings where K+ATP opening is partially compromised.
Predicting survival in hepatitis B
Authors: M Sherman
Journal: Gut (2005)

Alanine aminotransferase (ALT) level alone is not an appropriate indication for therapy in chronic hepatitis B infection, and other criteria in addition to ALT must be used to determine eligibility for therapy

Predictors of survival in chronic hepatitis B infection are surprisingly not well described. Various studies have identified different factors that were associated with adverse outcomes. For example, Niederau and colleagues,1 in a cohort of European patients, identified lack of clearance of hepatitis B e antigen (HBeAg) as a predictor of decreased survival. Others have identified older age, presence of cirrhosis, and the persistence of alanine aminotransferase (ALT) elevations as adverse prognostic signs in an antibody to hepatitis B e antigen (anti-HBe) positive cohort.2 In patients undergoing a flare of hepatitis B activity, whether spontaneous or chemotherapy induced, the presence of jaundice is an ominous sign.3 None of these adverse predictive factors are unexpected. Clearly, jaundice, cirrhosis, older age, and elevated ALT are obvious adverse predictive factors but until recently we have not had the tools to predict, years in advance, the outcome of chronic hepatitis B infection. This is important because we would prefer to offer treatment only to those who are likely to develop complications of the disease, and not to those whose disease will become inactive without long term sequelae. Recently, new predictors of outcome have been identified. At last year’s American Association for Study of Liver Disease (AASLD) meeting and the recent European Association for Study of the Liver (EASL) meeting, new data were presented that contribute to this debate. In addition, the article by Yuen and colleagues4 in this issue of Gut also forces us to re-examine some of our assumptions about hepatitis B prognosis and therefore treatment (see page 1610) .

To some extent our current management algorithms …
Characterization of a novel and potent collagen antagonist, caffeic acid phenethyl ester, in human platelets: In vitro and in vivo studies
Authors: G HSIAO, J LEE, K LIN, C SHEN, T FONG, D CHOU, J SHEU
Journal: Cardiovascular Research (2007)

Objective Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of honeybee hives, has been demonstrated to possess multiple pharmacological activities. In the present study, CAPE (6–25 μM) specifically inhibited collagen-induced platelet aggregation and the ATP release reaction in platelet suspensions.
Tumor and Vascular Targeting of a Novel Oncolytic Measles Virus Retargeted against the Urokinase Receptor
Authors: Yuqi Jing, Caili Tong, Jin Zhang, Takafumi Nakamura, Ianko Iankov, Stephen J. Russell, Jaime R. Merchan
Journal: Cancer Research (2009)

Oncolytic measles virus (MV) induces cell fusion and cytotoxicity in a CD46-dependent manner. Development of fully retargeted oncolytic MVs would improve tumor selectivity. The urokinase-type plasminogen activator receptor (uPAR) is a tumor and stromal target overexpressed in multiple malignancies. MV-H glycoproteins fully retargeted to either human or murine uPAR were engineered and their fusogenic activity was determined. Recombinant human (MV-h-uPA) and murine (MV-m-uPA) uPAR-retargeted MVs expressing enhanced green fluorescent protein (eGFP) were rescued and characterized. Viral expression of chimeric MV-H was shown by reverse transcription-PCR and Western blot. In vitro viral replication was comparable to MV-GFP control. The receptor and species specificity of MV-uPAs was shown in human and murine cells with different levels of uPAR expression. Removal of the NH(2)-terminal fragment ligand from MV-uPA by factor X(a) treatment ablated the MV-uPA functional activity. Cytotoxicity was shown in uPAR-expressing human and murine cells. MV-h-uPA efficiently infected human endothelial cells and capillary tubes in vitro. I.v. administration of MV-h-uPA delayed tumor growth and prolonged survival in the MDA-MB-231 breast cancer xenograft model. Viral tumor targeting was confirmed by immunohistochemistry. MV-m-uPA transduced murine mammary tumors (4T1) in vivo after intratumor administration. MV-m-uPA targeted murine tumor vasculature after systemic administration, as shown by dual (CD31 and MV-N) staining of tumor capillaries in the MDA-MB-231 model. In conclusion, MV-uPA is a novel oncolytic MV associated with potent and specific antitumor effects and tumor vascular targeting. This is the first retargeted oncolytic MV able to replicate in murine cells and target tumor vasculature in a uPAR-dependent manner.
Sorafenib in Patients with Advanced Non-small Cell Lung Cancer that Harbor K-Ras Mutations: A Brief Report
Authors: Egbert F. Smit, Anne-Marie C. Dingemans, Frederik B. Thunnissen, Monique M. Hochstenbach, Robert-Jan van Suylen, Pieter E. Postmus
Journal: Journal of Thoracic Oncology (2010)
Utilization of an Operant Conditioning Model for the Treatment of Character and Behavior Disorders in a Military Setting
Authors: ARTHUR D. COLMAN, STEWART L. BAKER
Journal: American Journal of Psychiatry (1969)

The operant conditioning model was applied to a ward program for delinquent military recruits diagnosed as having character and behavior disorders. Early findings reported here indicate that the program has been quite successful in helping such men adjust to Army requirements and return to regular military duty.
Reproductive Factors, Hormone Use, Estrogen Receptor Expression and Risk of Non–Small-Cell Lung Cancer in Women
Authors: Ann G. Schwartz, Angela S. Wenzlaff, Geoffrey M. Prysak, Valerie Murphy, Michele L. Cote, Sam C. Brooks, Debra F. Skafar, Fulvio Lonardo
Journal: Journal of Clinical Oncology (2007)

Purpose Estrogen receptor (ER) expression in lung tumors suggests that estrogens may play a role in the development of lung cancer. We evaluated the role of hormone-related factors in determining risk of non–small-cell lung cancer (NSCLC) in women. We also evaluated whether risk factors were differentially associated with cytoplasmic ER-α and/or nuclear ER-β expression–defined NSCLC in postmenopausal women. Patients and Methods Population-based participants included women aged 18 to 74 years diagnosed with NSCLC in metropolitan Detroit between November 1, 2001 and October 31, 2005. Population-based controls were identified through random digit dialing, matched to patient cases on race and 5-year age group. Interview data were analyzed for 488 patient cases (241 with tumor ER results) and 498 controls. Results Increased duration of hormone replacement therapy (HRT) use in quartiles was associated with decreased risk of NSCLC in postmenopausal women (odds ratio = 0.88; 95% CI, 0.78 to 1.00; P = .04), adjusting for age, race, pack-years, education, family history of lung cancer, current body mass index, years exposed to second-hand smoke in the workplace, and obstructive lung disease history. Among postmenopausal women, ever using HRT, increasing HRT duration of use in quartiles, and increasing quartiles of estrogen use were significant predictors of reduced risk of NSCLC characterized as ER-α and/or ER-β positive. None of the hormone-related variables were associated with nuclear ER-α–or ER-β–negative NSCLC. Conclusion These findings suggest that postmenopausal hormone exposures are associated with reduced risk of ER-α–and ER-β–expressing NSCLC. Understanding tumor characteristics may direct development of targeted treatment for this disease.
Ischemic and Thrombotic Effects of Dilute Diesel-Exhaust Inhalation in Men with Coronary Heart Disease
Authors: Nicholas L. Mills, Håkan Törnqvist, Manuel C. Gonzalez, Elen Vink, Simon D. Robinson, Stefan Söderberg, Nicholas A. Boon, Ken Donaldson, Thomas Sandström, Anders Blomberg, David E. Newby
Journal: New England Journal of Medicine (2007)

Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function.