tbuckley/cabot-search huggingface dataset:
siRNA for p53R2 inhibits increases in p53R2 expression following exposure to DNA damaging agents.
Authors: Joe Barber, Donna S. Shewach
Journal: Cancer Research (2006)

5509   Gemcitabine (2′, 2′-difluoro-2′-deoxycytidine, dFdCyd) is a clinically effective chemotherapeutic agent and radiation sensitizer. These properties require intracellular phosphorylation of dFdCyd to its di- and triphosphate metabolites. dFdCTP is incorporated into DNA and is primarily responsible for cytotoxicity, whereas inhibition of ribonucleotide reductase by dFdCDP correlates strongly with radiosensitization. Ribonucleotide reductase is the enzyme responsible for converting ribonucleotide diphosphates to their corresponding deoxynucleotide forms. It is the rate-limiting step in the de novo synthesis of DNA. It is a tetrameric protein consisting of two regulatory (R1) and two catalytic (R2) subunits. Recently, a novel ribonucleotide reductase subunit, p53R2, was discovered. p53R2 is a homologue of the R2 subunit, and it has been shown to be activated in a p53-dependent fashion following DNA damage and combine with R1 to provide deoxynucleotides for DNA repair. In this study, we wished to examine the effects of inhibition of p53R2 on other proteins. Since there are no specific inhibitors of p53R2 that do not inhibit R2 activity, we utilized the siRNA approach to specifically decrease p53R2 expression. MCF-7 breast cancer cells treated with dFdCyd at concentrations ranging from 10 nm to 300 nm exhibited a significant increase in p53R2 expression within 2 hr after drug addition as demonstrated by Western blot analysis, and p53R2 expression remained elevated for at least 72 hr. Transfection of p53R2 siRNA inhibited p53R2 activity following a 24 h exposure to dFdCyd as early as 48 h post-transfection. p53R2 expression was inhibited following a 24 h exposure to dFdCyd for at least 120 h post-transfection. There was no change in p53R2 expression following the use of non-specific siRNA, or through mock transfection. Importantly, the siRNA transfection did not decrease R2 expression. Also, no there were no observed chances in p53 expression. Thus, the siRNA approach provides an excellent mechanism for determining the contribution of p53R2 separately from that of R2, and may provide important information on the roles of these proteins in the cytotoxicity and radiosensitization by dFdCyd.
The role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes: Are we getting closer?
Authors: Stewart J. Levine, Sally E. Wenzel
Journal: Annals of Internal Medicine (2010)

New therapeutic approaches are needed for severe asthmatics who are refractory to standard therapy with high doses of inhaled corticosteroids plus long-acting β2-agonists. Current treatment guidelines for severe asthmatics from the National Asthma Education and Prevention Program recommend the addition of oral corticosteroids, which are associated with significant morbidity, and for those with allergic asthma, anti-IgE. Genetic and translational studies, as well as clinical trials, suggest that in a sub-group of patients the pathobiology of severe asthma is mediated by immune pathways driven by Th2-type CD4+ T cells which produce a characteristic repertoire of interleukins, including IL-4, IL-5 and IL-13. Therefore, biological modifiers of Th2-type interleukins, such as monoclonal antibodies, soluble receptors and receptor antagonists, represent a rational strategy for developing new treatment approaches, but will need to be targeted to selected individuals in whom the appropriate Th2 immune pathway is “active.” The benefits of immune modifier therapies targeting Th2-type cytokines, however, will need to be weighed against the toxicities associated with inhibition of key biological pathways, as well as the expense of future medications. Therefore, future clinical trials will need to clearly establish the efficacy and safety of biological modifiers of Th2 immune pathways before these approaches can enter routine clinical practice for the treatment of severe asthma.
Abstract 2713: MOG1 Mutations Associated With Brugada Syndrome Electrocardiogram Pattern
Authors: Darouna Kattygnarath, Svetlana Maugenre, Nathalie Neyroud, Guillaume Duthoit, Isabelle Denjoy, Raphael P Martins, Bernard Hainque, Francoise Hidden-Lucet, Alain Coulombe, Stephane N Hatem, Pascale Guicheney
Journal: Circulation (2009)

Purpose: Brugada syndrome (BrS) is a genetic disorder associated with arrhythmias and sudden cardiac death (SCD), caused mainly by mutations in the  SCN5A  gene, encoding the  α  subunit of the cardiac sodium channel, Nav1.5. Most mutations lead to a loss of function, characterized by reduced sodium current density. However, less than 30% of probands have  SCN5A  mutations, suggesting that other genes are implicated. MOG1 has recently been identified as a new co-factor of Nav1.5, potentially regulating sodium channel expression and trafficking. Therefore, we hypothesized that mutations in  MOG1  may be related to BrS.  Methods:  MOG1  was screened by direct sequencing in 190 BrS patients who were negative for  SCN5A  mutations. Functional effects were investigated by using whole-cell patch-clamp techniques in stably expressing Nav1.5 HEK293 cells, transiently transfected with wild-type (WT) or mutant MOG1 or empty vector (control cells, CT).  Results: Genetic screening revealed two mutations, c.181G > T (p. E61X) and c.249G > C (p. E83D). The nonsense mutation was found in an asymptomatic male patient with a type-1 BrS ECG pattern, parietal block, and sustained polymorphic ventricular tachyarrhythmia with programmed stimulation. The missense mutation was carried by a symptomatic female patient who also had a type-1 BrS ECG pattern and a resuscitated SCD after overdose. She died 4 days later without further investigations. In cells, overexpression of WT MOG1 significantly increased sodium current density compared to CT cells (INa : CT −91.2+/− 17.3 pA/pF n = 14; MOG1 WT −185.3 +/− 42.0 pA/pF n = 12; p* = 0.039), while this effect was not observed with the p. E83D mutant (INa: MOG1 E83D −89.5 +/−28.4 pA/pF n = 12). No differences in biophysical properties of the sodium channel (activation/inactivation) were detected.  Conclusion: We provide for the first time clinical and molecular evidence implicating  MOG1  in patients displaying BrS ECG patterns. Electrophysiological studies on p. E83D MOG1 mutant protein demonstrated a loss of function in sodium current density suggesting that mutant protein may alter normal expression and/or trafficking of Nav1.5. Our findings support  MOG1  as a new suceptibility gene for life-threatening ventricular arrhythmias.
Abstract P249: A Behavioral Weight Loss Intervention is Effective for Change in CVD Risk Factors in Young Adults: The IDEA Study
Authors: John M Jakicic, Kelliann K Davis, Bethany Barone Gibbs, Diane Helsel, Wendy C King, Amy D Rickman, Renee J Rogers, Abdus Wahed, Steven H Belle
Journal: Circulation (2015)

Introduction: Few studies have examined behavioral weight loss interventions with respect to change in cardiovascular disease risk factors in young adults (aged 18 to 35 years). Hypothesis: We tested the hypothesis that a 6 month behavioral weight loss intervention resulted in significant improvements in selective cardiovascular disease risk factors in young adults. Methods: Data are presented as median [25 th , 75 th percentiles]. 470 participants (age: 30.9 [27.8, 33.7] years); BMI: 31.2 [28.4, 34.3] kg/m 2 ) were enrolled in a 6 month behavioral weight loss intervention that included weekly group sessions and prescribed an energy restricted diet and moderate-to-vigorous physical activity. Assessments included weight using a standardized protocol, resting blood pressure, and fasting lipids, glucose, and insulin. Statistical significance of change was according to tests of symmetry or the Wilcoxon matched pairs signed ranks test. Results: The primary outcome (weight) was available for 424 of the 470 participants (90.2%). Weight significantly decreased (-7.8 kg [-12.2, -3.7]) (p&lt;0.0001). Systolic (-4.0 mmHg [-8.5, 0.5] and diastolic blood pressure (-3.0 mmHg [-6.5, 1.0]) decreased (p&lt;0.0001). Total cholesterol (-13 mg/dl [-28.0, 2.0]), LDL cholesterol (-9.5 mg/dl [-21.7, 2.0]), triglycerides (-8.5 mg/dl [-44.0, 9.0]), glucose (-4.0 mg/dl [-8.0, 1.0]), and insulin (-2.6 mIU/L [-5.9, 0.7]) decreased (p&lt;0.0001, n=416). There was not a significant change in HDL cholesterol (p=0.72). Conclusions: In conclusion, after 6 months, weight loss was observed in young adults assigned to this behavioral intervention that focused on physical activity and diet modification. They tended to also have improved cardiovascular disease risk factors. This may demonstrate an approach to reducing cardiovascular disease risk in young adults. Supported by NIH (U01HL096770) and AHA (12BGIA9410032)
Women take four top jobs in health and social care in Wales
Authors: Roger Dobson
Journal: BMJ (2001)

Ann Lloyd has been appointed the new NHS director in Wales. Her appointment means that women now occupy all four top positions in health and social care in the principality.

Ms Lloyd, aged 53, a former chief executive of Frenchay Healthcare NHS Trust in Bristol, is part of a team that includes Jane Hutt (the Assembly health secretary), Dr …
Current Status of Hepatic Arterial Infusion Chemotherapy
Authors: Shuntaro Obi, Shinpei Sato, Toshihiro Kawai
Journal: Liver Cancer (2015)

Background: Hepatic arterial infusion chemotherapy (HAIC) is frequently used to treat advanced hepatocellular carcinoma (HCC) in Asian countries. However, there is a lack of evidence supporting the use of HAIC. Summary: Many studies report high response rates in patients with advanced HCC receiving HAIC, and clinical responses translate to survival benefits. Therefore, prediction of an antitumor response is important in selecting appropriate treatments. There are no proven post-sorafenib therapeutic measures or procedures for HCC patients with poor liver function, and HAIC is one of the few options for patients in these situations. Despite studies showing its effectiveness, the use of HAIC for treatment of advanced HCC is unclear because convincing data from large-scale randomized clinical trials are lacking. For HAIC to become a standard treatment for HCC, such trials must establish its efficacy compared with other HCC therapies; prediction of antitumor response in HAIC may aid trial design, and a multi-center, open-labelled, randomized clinical trial of HAIC in advanced HCC is currently in progress. Optimization of HCC treatment protocols and regimens is also required. Key message: We think that both HAIC and sorafenib are effective treatments for advanced HCC, and this review presents evidence supporting this contention.
Adenocarcinoma of the Cervix Uteri and Endometrium Combined With the Kartagener Syndrome on FDG PET/CT
Authors: Yin Zhang, Yue Chen, Zhanwen Huang, Fan Zhou
Journal: Clinical Nuclear Medicine (2015)

A 45-year-old woman with pathologically confirmed adenocarcinoma of the cervix uteri and endometrium underwent FDG PET/CT for staging. No metastasis was found. However, the images revealed bronchiectasis, sinusitis, and situs inversus totalis, which are the triad of Kartagener syndrome.
Abstract 2464: Severity of Obstructive Sleep Apnea Dependent upon Aldosterone Status in Subjects with Resistant Hypertension
Authors: Carolina C Gonzaga, Krishna K Gaddam, Eduardo Pimenta, David A Calhoun
Journal: Circulation (2008)

Background: Obstructive sleep apnea (OSA) and hyperaldosteronism are common in subjects with resistant hypertension. Prior results from our laboratory relate severity of OSA to aldosterone levels in patients with resistant hypertension suggesting that the 2 disease entities may be mechanistically linked. Objective: This study prospectively evaluated the relation between OSA severity and aldosterone status in subjects with resistant hypertension. Methods: One hundred nine consecutive subjects (age 55.9±9.3 years; 50% male) with resistant hypertension referred to a university clinic for resistant hypertension were prospectively evaluated with plasma renin activity (PRA), plasma aldosterone concentration, and 24-hr urinary aldosterone excretion. Hyperaldosteronism was defined as a PRA &lt;1.0 ng/mL/hr and 24-h urinary aldosterone excretion ≥ 12 μg/24-hr. Remaining patients were considered as having normal-aldosterone status. All subjects were evaluated by full-night attended diagnostic polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 events/hr. Results : Hyperaldosteronism was present in 28% of subjects. Overall, OSA was diagnosed in 77% of subjects; 81% of the high-aldosterone and 74% of the normal-aldosterone subjects. In subjects with hyperaldosteronism, plasma aldosterone and urinary aldosterone excretion correlated with AHI (r = 0.723, p &lt;0.001 and r = 0.639, p &lt;0.001, respectively) but not in the normal-aldosterone subjects (r = 0.008, p = 0.94 and r = 0.042, p = 0.71 respectively). Atrial natriuretic peptide (ANP) levels were significantly higher in the high-aldosterone compared to normal-aldosterone subjects (89±57 vs. 67±102 pg/ml; p = 0.03). Conclusion: OSA is extraordinarily common in patients with resistant hypertension. A significant correlation between both plasma and urinary aldosterone levels and severity of OSA is observed in high-aldosterone but not normal-aldosterone subjects. The higher level of ANP in high-compared to normal-aldosterone subjects suggests greater intravascular fluid retention in the former subjects. These results suggest worsening of OSA in patients with hyperaldosteronism secondary to chronic aldosterone-induced intravascular fluid retention.
Abstract 3603: SIRT1, a Stress-responsive Deacetylase is Required for Development of Compensatory Cardiac Hypertrophy
Authors: Nagalingam R Sundaresan, Sadhana A Samant, Ayman Isbatan, Vinodkumar B Pillai, Pv Ravindra, Senthilkumar B Rajamohan, Madhu Gupta, Mahesh P Gupta
Journal: Circulation (2009)
Abstract 2774: Six-Month IVUS Analysis of Long Coronary Artery Lesions Treated with Biolimus-A9 Eluting XTENT interdigitating stent with bioabsorbable polymer: Results of the CUSTOM II Trial
Authors: Takao Shimohama, Junya Ako, Ali Hassan, Yasuhiro Honda, Eberhard Grube, Peter J Fitzgerald
Journal: Circulation (2007)

Background: Multiple overlapping drug-eluting stents have been used to treat diffuse coronary disease; however, this approach is associated with increased incidence of adverse cardiac events and target lesion revascularization (TLR). The XTENT platform consists of Biolimus-A9 eluting stent on a bioabsorbable polymer with an interdigitating design, which allows operators to customize stent length in 6 mm cobalt-chromium modular units. The aim of this IVUS study was to evaluate the efficacy of the XTENT in the treatment of long lesions. Methods: Data were obtained from the CUSTOM II trial, a prospective, multicenter study, to assess the safety and efficacy of this stent system. Thirty patients (39 lesions) were available, with 6 months follow-up IVUS analysis, including 25 serial lesions. Lesions were divided into 2 groups: short (&lt;24 mm, n=13) and long (≥ 24 mm, n=12). Volumetric and/or cross-sectional analyses were performed. Each volume index was calculated as volume divided by stent length. Percent neointimal volume (%NIV) was calculated as (neointimal volume/stent volume) X100. Results: Baseline and 6 months follow-up IVUS data are shown in Table . Despite very long lesions and stent length (34.4±9.5 mm and 42.5±7.7 mm, respectively), % neointimal volume was &lt; 10%, even in the long lesion group. There were no differences in plaque volume index and vessel volume index at 6 months follow-up between the long and short lesion groups. One case with partial separation between the segments was found at follow-up in the long lesion group, but no lumen loss at the separation was observed. There was one TLR case in each group, but no cardiac death, AMI, and late-acquired incomplete stent apposition (ISA) in either group. Conclusions: The XTENT stent demonstrated excellent suppression of neointimal hyperplasia in long coronary artery lesions at 6 months follow-up. This stent system may offer an option for treatment of complex diffuse lesions.
Abstract 4606: Vascular Responses and Differential Mechanisms of Late Stent Thrombosis Following Sirolimus- and Paclitaxel- Eluting Stents in Humans
Authors: Gaku Nakazawa, Aloke V Finn, Marc Vorpahl, Elena Ladich, Frank D Kolodgie, Renu Virmani
Journal: Circulation (2009)

Background Clinical trials have reported differences in late lumen loss between sirolimus-(SES) and paclitaxel-(PES) drug-eluting stents (DES). However, differences in the vascular response, time course of healing, and mechanisms of late stent thrombosis (LST) between SES and PES remain unknown.  Methods From CVPath autopsy registry, 174 cases (230 DES lesions) were analyzed. Morphometric analysis was performed in 127 cases (171 lesions) who died ≥30days after stenting. Morphometric and histologic findings such as fibrin deposition, endothelial strut coverage, inflammatory response, and mechanisms of thrombosis were recorded.  Results The frequency of LST was similar between SES and PES (21% vs. 27%, p=0.47). However, the underlying mechanism was significantly different as localized hypersensitivity reaction was exclusively observed in SES while LST with malapposition and excessive fibrin deposition was only seen in PES. Neointimal thickness was greater in PES (0.13mm[0.03–0.20]) than SES (0.10mm[0.04–0.15], p=0.04), and both DES without stent thrombosis were associated with an increase in neointimal thickness over time (Figure). While both DES showed near complete strut coverage after 12months for “on-label” usage, the majority of stents placed for “off-label” indications remained unhealed beyond 12months in both DES (Figure).  Conclusion In this autopsy study, the mechanisms of LST were significantly different between SES and PES. Furthermore, DES placed for “on-label” indications demonstrated near complete healing after 12months, whereas DES placed for “off-label” indications remained unhealed.
Early Safety and Efficacy of Percutaneous Left Atrial Appendage Suture Ligation
Authors: Matthew J. Price, Douglas N. Gibson, Steven J. Yakubov, Jason C. Schultz, Luigi Di Biase, Andrea Natale, J. David Burkhardt, Ashish Pershad, Timothy J. Byrne, Brett Gidney, Joseph R. Aragon, Jeffrey Goldstein, Kriegh Moulton, Taral Patel, Bradley Knight, Albert C. Lin, Miguel Valderrábano
Journal: Journal of the American College of Cardiology (2014)
COLONIES FOR EPILEPTICS.
Authors: R Moore
Journal: JAMA (1906)

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 13121: Different Presentation Mode of Acute Myocardial Infarction is Associated With Antecedent Therapy With Nitrates and β-blockers
Authors: Sunao Kojima, Hisao Ogawa
Journal: Circulation (2014)

Introduction: Brief episodes of ischemia increases cardiac tolerance to a subsequent major ischemic insult. Prehospital medication may affect the mode of presentation in acute myocardial infarction (AMI) and pharmacologically precondition the heart toward ischemic episodes. Hypothesis: We assessed the hypothesis that antecedent therapy confers cardioprotection in patients suffering an AMI. Methods: The Japanese Acute Coronary Syndrome Study (JACSS) is a retrospective and multicenter observational study that is being conducted at 35 medical institutions in Japan. The JACSS database includes information on consecutive 1,204 patients who were hospitalized within 48 hours after the onset of AMI. Results: A total of 1,010 ST-elevation myocardial infarction (STEMI) and 194 non STEMI (NSTEMI) patients were included and the differences of the mode of presentation, prehospital medication and coronary risk factors were investigated in the present study. Coronary risk factors such as sex, hypertension, diabetes mellitus, hypercholesterolemia, smoking, obesity and previous coronary artery disease were comparable between STEMI and NSTEMI groups. Prehospital medication with aspirin, nitrates, β-blockers and calcium-channel blockers but not with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and statins were associated with the onset as NSTEMI. A stepwise regression analysis including coronary risk factors and prehospital medication revealed that chronic therapy with nitrates and β-blockers reduced the onset as STEMI compared with that as NSTEMI (table) Conclusions: Antecedent therapy with nitrates and β-blockers was associated with reduced severity of myocardial injury in response to an acute coronary event. Our findings may help to explain the missing link between a shift away from STEMI in favor of NSTEMI and a combined capability of nitrates and β-blockers to act as pharmacological inducers of ischemic preconditioning.
Abstract 12304: Impact of Coronary Artery Bypass Surgery in Patients With Ischemic Heart Failure: 5-Year Outcomes of the CREDO-Kyoto PCI/CABG Registry Cohort-2
Authors: Akira Marui, Takeshi Kimura, Hiroki Shiomi, Shiro Tanaka, Michiya Hanyu, Tatsuhiko Komiya, Toru Kita, Ryuzo Sakata, Cabg Registry Cohort Investigators
Journal: Circulation (2013)

Background: Ischemic heart disease is a major risk factor for heart failure. However, long-term benefit of PCI or CABG on ischemic heart failure with complex coronary disease has not been well eluc...
Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma
Authors: Nemanja Rodić, Jared P Steranka, Alvin Makohon-Moore, Allison Moyer, Peilin Shen, Reema Sharma, Zachary A Kohutek, Cheng Ran Huang, Daniel Ahn, Paolo Mita, Martin S Taylor, Norman J Barker, Ralph H Hruban, Christine A Iacobuzio-Donahue, Jef D Boeke, Kathleen H Burns
Journal: Nature Medicine (2015)
Use of multilocus variable-number tandem repeat analysis (MLVA) in eight European countries, 2012
Authors: B A Lindstedt, M Torpdahl, G Vergnaud, S Le Hello, F  X Weill, E Tietze, B Malorny, D M Prendergast, E Ní Ghallchóir, R F Lista, L  M Schouls, R Söderlund, S Börjesson, S Åkerström
Journal: Eurosurveillance (2013)

Genotyping of important medical or veterinary prokaryotes has become a very important tool during the last decades. Rapid development of fragment-separation and sequencing technologies has made many new genotyping strategies possible. Among these new methods is multilocus variable-number tandem repeat analysis (MLVA). Here we present an update on the use of MLVA in eight European countries (Denmark, France, Germany, Ireland, Italy, the Netherlands, Norway and Sweden). Researchers in Europe have been active in developing and implementing a large array of different assays. MLVA has been used as a typing tool in several contexts, from aiding in resolving outbreaks of foodborne bacteria to typing organisms that may pose a bioterrorist threat, as well as in scientific studies.