tbuckley/cabot-search huggingface dataset:
Abstract 16419: A Comparative Analysis of Prasugrel versus Ticagrelor on Rates of High On-Treatment Platelet Reactivity Following Switch From Clopidogrel Therapy
Authors: Fabiana Rollini, Jung Rae Cho, Francesco Franchi, Mona Bhatti, Christopher DeGroat, Mohamad Taha, Ana Muniz-Lozano, Kamaldeep Singh, Elisabetta Ferrante, Elizabeth C Dunn, Martin M Zenni, Luis A Guzman, Theodore A Bass, Dominick J Angiolillo
Journal: Circulation (2014)

Background: Clopidogrel is characterized by non-uniform pharmacodynamic (PD) effects leading to considerable rates of high on-treatment platelet reactivity (HPR), a marker of increased atherothrombotic risk. Prasugrel and ticagrelor have greater potency and more uniform PD effects compared with clopidogrel. The effects of switching from clopidogrel to prasugrel or ticagrelor and how this impacts HPR rates has been poorly explored. Methods: This was a prospective, randomized PD study conducted in patients with coronary artery disease on maintenance aspirin (81mg/qd) and clopidogrel (75mg/qd) therapy. Patients were randomized to switch to prasugrel (60mg loading dose/10mg maintenance dose qd) or ticagrelor (180mg loading dose/90mg maintenance dose bid) for 1 week. PD assessments were performed at 5 time points: before (while on clopidogrel) and 30 min, 2 hrs, 24 hrs and 1 week after switch. HPR was defined by a platelet reactivity index (PRI) &gt; 50% assessed by VASP and platelet reaction unit (PRU) &gt; 208 assessed by VerifyNow P2Y12 (VN). Results: A total of 110 patients were studied. HPR on clopidogrel therapy as defined by VASP-PRI was observed in 67.3% of the overall population. HPR rates were similarly distributed among patients subsequently randomized to prasugrel vs ticagrelor (69.8% vs 64.7%, p=0.57). After switching to prasugrel or ticagrelor, HPR rates significantly reduced as early as 30 min and continued to decrease consistently in both groups over the study time period. At 1 week, HPR was found in 13.7% and 15.6% of patients randomized to prasugrel and ticagrelor, respectively (p=0.80) (Figure). Parallel findings were observed when assessing HPR rates defined by VN-PRU (Figure). Conclusions: Switching from clopidogrel to a more potent P2Y 12 inhibiting agent significantly reduces HPR rates. Reduction in HPR rates occur to a similar extent between prasugrel and ticagrelor in both the acute and maintenance phases of therapy.
Expanding Statin Use to Help More At-Risk Patients Is Causing Financial Heartburn
Authors: Mike Mitka
Journal: JAMA (2003)

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
Abstract 1780: Identification and characterization of L524-0366 as a small molecule inhibitor that disrupt TWEAK-Fn14 signaling in glioblastoma
Authors: Harshil D. Dhruv, Joseph C. Loftus, Pooja Narang, Joachim L. Petit, Donald Chow, Holly Yin, Michael Berens, Nathalie Meurice, Nhan L. Tran
Journal: Cancer Research (2014)

Abstract Deregulation of the TWEAK-Fn14 signaling pathway is observed in many diseases including inflammation, autoimmune diseases, and cancer, notably glioblastoma. Activation of Fn14 signaling by TWEAK binding triggers glioma cell invasion and survival and therefore represents an attractive pathway for therapeutic intervention. Based on structural studies of the TWEAK-binding cysteine rich domain of Fn14, several homology models of TWEAK were built to investigate plausible modes of TWEAK-Fn14 interaction. Two promising models, centered on different anchoring residues of TWEAK [Tyrosine 176 (Y176) and Tryptophan 231 (W231)], were prioritized using a data-driven strategy. Site-directed mutagenesis of TWEAK at Y176, but not W231, resulted in the loss of TWEAK binding to Fn14 substantiating Y176 as the anchoring residue. Importantly, mutation of TWEAK at Y176 did not disrupt TWEAK trimerization, but failed to induce Fn14 mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. The validated structural models were utilized in a virtual screen to design a targeted library of small molecules predicted to disrupt the TWEAK-Fn14 interaction. 129 small molecules were screened iteratively, with identification of molecules producing up to 37% inhibition of TWEAK-Fn14 binding. One specific compound, L524-0366 binds specifically to the Fn14 receptor and disrupt TWEAK-Fn14 interaction. Treatment of L524-0366 suppresses TWEAK-induced cell migration and survival in glioblastoma cells. In summary, we present a data-driven in silico study revealing key structural elements of the TWEAK-Fn14 interaction, followed by experimental validation, serving as a guide for the design of small molecule inhibitors of the TWEAK-Fn14 ligand-receptor interaction. Our results provide the foundation for further exploration utilizing L524-0366 as a small molecule inhibitor to the TWEAK-Fn14 signaling axis. Citation Format: Harshil D. Dhruv, Joseph C. Loftus, Pooja Narang, Joachim L. Petit, Donald Chow, Holly Yin, Michael Berens, Nathalie Meurice, Nhan L. Tran. Identification and characterization of L524-0366 as a small molecule inhibitor that disrupt TWEAK-Fn14 signaling in glioblastoma. [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 1780. doi:10.1158/1538-7445.AM2014-1780
Abstract 9658: Generation Differences in Long-Term Clinical Outcomes in Diabetic Patients After PCI Across POBA-, BMS- and DES-Era
Authors: Ryo Naito, Katsumi Miyauchi, Hirokazu Konishi, Shuta Tsuboi, Manabu Ogita, Takatoshi Kasai, Hiroshi Tamura, Shinya Okazaki, Hiroyuki Daida
Journal: Circulation (2014)

Introduction: PCI has evolved with technological advance, improvement of operators’ techniques and medical therapy for secondary prevention. Despite these improvements, diabetes remains a negative predictor. To date, little is known regarding improvement of clinical outcomes in diabetic patients with PCI. We examined a temporal trend of long-term clinical outcomes in diabetic cohort across the different generations. Hypothesis: We hypothesized that clinical outcomes would improve with advances of PCI. Methods: We analyzed data of diabetic patients with PCI in Juntendo University from 1984 to 2010. The patients were divided into three groups according to the procedure data (POBA-era; January 1984 - December 1997, BMS-era; January 1998 - July 2004 and DES-era; August 2004 - February 2010). Primary endpoint was a composite of major adverse cardiovascular events including all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and revascularization. Results: A total of 1544 patients were examined (POBA-era; 374, BMS-era; 494 and DES-era; 676). The mean age was higher in DES-era. A higher prevalence of hypertension and dyslipidemia was observed in DES-era. The success rate of PCI was lower among the patients in POBA-era. Kaplan-Meier estimation for 3-year MACE was significantly different among the eras (Figure 1). Multivariable Cox regression analysis showed that DES-era was a predictor for long-term MACE (DES- vs BMS era; HR 0.50, 95%, CI 0.38 - 0.66, P &lt; 0.001, DES- vs POBA-era; HR 1.60, 95% CI 0.34-27.9, P = 0.6). Conclusions: Long-term clinical outcomes in diabetic patients who underwent PCI were more favorable in DES-era, despite the higher risk profiles.
DNA breakage by tallysomycin.
Authors: J E Strong, S T Crooke
Journal: Cancer Research (1978)

Abstract  Tallysomycin, a third generation bleomycin analog was found to be more potent than bleomycin in the Walker 256 carcinosarcoma and the P-388 leukemia tumor systems and against a variety of bacteria and fungl. The mechanism of action of tallysomycin appears to be similar to that of bleomycin. Both drugs induced strand scission of isolated purified DNA and intracellular DNA. Breakage of DNA was determined by using three systems: PM-2 DNA fluorescence assay, agarose gel electrophoresis of PM-2 DNA, and alkaline sucrose density gradient sedimentation of Novikoff hepatoma cellular DNA. The optimum pH (9.5), the reducing agent concentration (25 mm 2-mercaptoethanol), and the incubation temperature (30–37°) were equivalent for both drugs for degradation of PM-2 DNA. Moreover, agarose gel electrophoresis demonstrated that both drugs induced both single- and double-strand breaks. However, tallysomycin had significantly less DNA breakage activity than had bleomycin.  Treatment of Novikoff hepatoma ascites cells in vitro with bleomycin or tallysomycin resulted in degradation of intracellular DNA demonstrated by alkaline sucrose density gradient centrifugation. However, tallysomycin was less potent in this system than was bleomycin. Since the difference in DNA breakage activity cannot be explained on the basis of trace metal (iron) contamination because tallysomycin had a greater iron concentration than had bleomycin, other factors are probably involved in the increased antitumor potency of tallysomycin than intrinsic DNA breakage activity.
Treating CS gas injuries to the eye
Authors: P. J Gray
Journal: BMJ (1995)

Treating CS gas injuries to the eye Exposure at close range is particularly dangerous EDr1OR,-Jean-Paul Yih's editorial on injuries to the eye caused by O-chlorobenzylidene malono- nitrile (CS) gas, or tear gas, draws attention to the short term effects of the gas on the eye and suggests that such injuries may well be a future problem as individual police officers in Britain will soon be carrying pocket aerosols of CS gas.' Yih implies that the ocular toxicity of CS gas is rapidly reversible; however, the ocular irritation from 1-chloroacetophenone (another tear gas agent) typically lasts only 15 minutes but may persist for up to three days.2The problems are particularly pronounced when the charge of tear gas is fired at close range: powder infiltration of the conjunctiva, cornea, and sclera will occur.The forces are so great that conjunctival tearing may occur.Corneal stromal oedema and later deep vascularisation may ensue, and a multitude of complications have been reported, including symblepharon, pseudopterygium, infective keratitis, trophic ketatopathy, posterior synechia, secondary glaucoma, cataracts, hyphaema, vitreous haemor- rhage, and traumatic optic neuropathy.' Thus
Thrombolysis in anterior myocardial-infarction-effect onregionnal viability studied with positron emission tomography
Authors: C. M. Delandsheere, D. Raets, Luc Pierard, Christian Berthe, Victor Legrand, Luc Crochelet, Jean-Paul Chapelle, C. Lemaire, G. Delfiore, M. Guillaume, D. Lamotte, Henri Kulbertus, Pierre Rigo
Journal: Circulation (1987)
Aggressive Behaviors and Injuries Among Nursing Home Residents
Authors: Barbara Herbert, Ylisabyth S Bradshaw
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
SPONTANEOUS PARTIAL OCCLUSION OF THE INNOMINATE ARTERY: REPORT OF A CASE WITH ANGIOCARDIOGRAPHIC CONFIRMATION
Authors: N P CHRISTY, L G LUBIC, M D YAHR
Journal: Annals of Internal Medicine (1954)

ExcerptThe clinical syndrome of carotid artery occlusion with resultant cerebral vascular insufficiency is well recognized, having been emphasized as long ago as 1914 by Hunt1 and more recently reviewed by Galdston and his associates.2 There are varied etiologic factors. Carotid arteriosclerosis with superimposed thrombosis is thought to be the commonest offender,2 while trauma,1 "serpentine" aneurysms3 and embolization1, 2, 4 have also been implicated. Signs of optic nerve damage on the side of the thrombosed vessel occurring together with contralateral hemiplegia should arouse suspicion of carotid artery occlusion.5, 6 Carotid angiography may confirm the clinical impression.7Disease of more proximal vessels,...
Abstract 73: Improving Teamwork Perceptions and Cardiopulmonary Resuscitation Performance by High-Fidelity Simulation-Based Teamwork Training
Authors: Eric H Chou, Chih-Wei Yang, Kah-Meng Chong, Huang-Fu Yeh, Edward P Huang, Cheng-Yi Wu, Hui-Chih Wang, Yueh-Ping Liu, Wen-Chu Chiang, Patrick C Ko, Matthew H Ma
Journal: Circulation (2011)

Introduction: The quality of cardiopulmonary resuscitation (CPR) performance influences patient's outcome. Besides individual technical knowledge and skills, teamwork perceptions have an impact on team performance, and consequently on resuscitation quality. This study aimed to investigate the impacts of high-fidelity simulation (HFS)-based teamwork training on team perceptions and CPR performance. Methods: This was a prospective, case-controlled study. A four-scenario, HFS-based teamwork training program was developed and implemented from November 2007 to February 2008. In addition to resuscitation skills, the program focused on teaching teamwork competencies, including leadership, communication, situation monitoring, and mutual support. Case scenarios were simulated using a high-fidelity mannequin simulator in a simulated emergency department (ED) setting. Audio-visual assisted feedback was given by facilitators after each scenario. A standardized questionnaire for assessment of teamwork performance was developed, using 5-point Likert scales. All participants completed the questionnaires immediately after each scenario, according to their performance during that simulation session. Both the first and last case scenarios were patients of out-of-hospital cardiac arrest. CPR performance including compression rate, no-flow ratio, and initiation time of defibrillation was measured by reviewing the videos. Results: A total of 83 ED staffs, including 24 residents and 59 nurses, were enrolled. Teamwork perceptions improved significantly after the simulation training course ( p &lt;0.001). For CPR performance, there was a trend toward decreased hyperventilation rate (19.1±5.6 vs. 14.8±8.2 min -1 , p =0.10), increased chest compression rate (102.4±17.1 vs. 110.4±15.2 min -1 , p =0.12), and faster initiation of defibrillation (93.4±26.9 vs. 69.1±39.0 secs, p =0.09) after the training course. No-flow fraction (0.23±0.07 vs. 0.17±0.08, p =0.01), initiation of intubation (99.1±40.6 vs. 77.0±37.0 secs, p =0.02) and intravenous access (86.9±37.7 vs. 63.4±33.8 secs, p =0.02) were significantly improved. Conclusion: HFS-based teamwork training is effective in improving teamwork perceptions and some aspects of CPR performance.
Antiproliferative effects of 7,8 diacetoxy 4 methyl coumarin and 7,8 diacetoxy 4 methyl thiocoumarin in human lung adenocarcinoma cell line
Authors: Anita Goel, Ashok Prasad, Virinder Parmar, Balram Ghosh, Neeru Saini
Journal: Clinical Cancer Research (2007)

C38   The availability of new and more effective anticancer drugs is considered to be the key for the achievement of a substantial improvement in the treatment of advanced non-small cell lung cancer (NSCLC). More hope lies in the isolation of bioactive phytochemicals from medicinal plants for their possible usefulness in the control of various ailments. Coumarins, naturally occurring benzopyrene derivatives have attracted intense interest in recent years because these have been identified from natural source, especially green plants and have diverse pharmacological activity. In the present study we examined the effect of antioxidant coumarin DAMC (7,8 Diacetoxy 4 methyl coumarin) and its thioderivative DAMTC (7,8 Diacetoxy 4 methyl thiocoumarin ) on human non small cell lung cancer A549 cells. We observed that both DAMC and DAMTC inhibit cellular proliferation in a dose dependent manner. These coumarin compounds also induce apoptosis as confirmed by annexin assay and cell cycle analysis. Induction of apoptosis occurs through mitochondrial mediated pathway as both DAMC and DAMTC caused the release of cytochrome c to the cytosol and activates caspase-9 without affecting the activity of caspase-8. Further studying the mechanism of action of these coumarin compounds we found that DAMC and DAMTC alters the expression of several genes (proapoptotic as well as antiapoptotic) as shown by western blot analysis. Our findings may offer new insight into the antiproliferative activity of DAMC and its thiocoumarin derivative DAMTC in A549 cells which will be important to fully exploit the potential of these drugs as chemotherapeutic agents.
High prevalence of undiagnosed airflow obstruction in patients with ischaemic heart disease
Authors: Fanny W.S. Ko, Yat Yin Lam, Bryan P.Y. Yan, JoJo H.Y. Chu, David S.C. Hui
Journal: European Respiratory Journal (2014)

Introduction: Cardiovascular disease (CVS) and chronic obstructive airway disease (COPD) share the common risk factor of smoking. It would be important and interesting to assess the prevalence of undiagnosed COPD in patients with pre-existing CVS disease.

Method: Patients underwent percutaneous coronary intervention (PCI) for ischaemic heart disease (IHD) between August 2009 and October 2010 with no history of obstructive lung disease (such as asthma, COPD, bronchiectasis) and aged ≥40 years were recruited. Spirometry examination was performed and blood biomarker ST2 (member of the interleukin 1 receptor family and a novel biomarker of cardiac stress) was assayed by enzyme linked immunosorbent assay.

Results: 475 subjects (mean age 64±9.7, range 40-85years, 414 males, 278 current or ex-smokers) underwent successful spirometry examination. 322(67.8%), 126(26.5%), 26(5.5%) and 1(0.2%) had interventions to 1, 2, 3 and 4 cardiac vessels respectively. 51 (10.7%) subjects had undiagnosed airflow obstruction with FEV1/FVC ratio <70%. Among these 51 subjects, 14(27.5%), 23(45.1%), 14(27.5%) had FEV1 ≥80, 50-80 and 30-50% predicted normal, respectively. ST2 levels were higher in subjects with poorer lung function amongst those with airflow obstruction (median[IQR] 36.76[19.51-48.36] vs 26.18[19.72-33.55]ng/ml for FEV1 30-50 vs ≥50% predicted normal, p=0.01).

Conclusion: Undiagnosed airflow obstruction is common among patients who had undergone PCI for IHD and more severe lung function impairment is associated with higher cardiac stress.
Canine Blastomycosis as a Harbinger of Human Disease
Authors: SAROSI GEORGE A.
Journal: Annals of Internal Medicine (1979)

Blastomycosis occurred in six patients in five households. In each instance one or more dogs living with the family or living near the family also developed blastomycosis. The recognition of canine blastomycosis helped in the early diagnosis of human cases. Because both dogs and patients were probably infected at the same place, canine blastomycosis may be an important epidemiologic marker, alerting physicians to the possible presence of concomitant blastomycosis in humans.
Role of the prolyl-isomerase Pin1 in cap-dependent translation and cell transformation
Authors: Mayuko Nishi, Ichiro Aoki, Akihide Ryo
Journal: Clinical Cancer Research (2006)

B9   Cap-dependent translation is a fundamental process of gene expression and plays a critical role in cell proliferation and oncogenesis. Cap-dependent translation is initiated by the assembly of the eukaryotic translation initiation factors, eIF4E, eIF4G and eIF4A to form the eIF4F complex, which is often dysregulated in many human malignancies. eIF4E is abnormally highly expressed in multiple human cancers including breast cancer and the overexpression of eIF4E alone can transform mammary epithelial cells. Recent reports also indicate that eIF4E is regulated by specific post-translational modifications such as phosphorylation. However, the subsequent biological effects following phosphorylation have not yet been characterized. We here report that the peptidyl prolyl-isomerase Pin1 regulates eIF4E activation in breast cancer cells. The use of 7-methyl-GTP pull-down analysis reveals that Pin1 is present in eIF4E complexes specifically in breast cancer cells. Pin1 directly binds eIF4E via its Thr9-Pro and Thr11-Pro motifs, and enhances the interaction of both eIF4E and eIF4G with 7-methyl-GTP, thereby facilitating cap-dependent translation. Moreover, the depletion of Pin1 by specific siRNA significantly suppresses eIF4E-mediated cell transformation. These results indicate that Pin1 plays a pivotal role in the inappropriate activation of translational regulation via eIF4E in breast cancer cells, which affects both cell proliferation and oncogenic transformation. Hence, Pin1 could be an intriguing anti-cancer target.
Generics Get Boost
Authors: Brian Vastag
Journal: JAMA (2003)

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