tbuckley/cabot-search huggingface dataset:
Critical role of Bax and Bak and reactive oxygen species in mitochondria-mediated apoptosis by garlic-derived cancer chemopreventive agent diallyl trisulfide
Authors: Young-Ae Kim, Dong Xiao, Hui Xiao, Anna Powolny, Karen Lew, Megan Reilly, Yan Zeng, Shivendra Singh
Journal: Cancer Research (2007)

21  Diallyl trisulfide (DATS), a cancer chemopreventive constituent of processed garlic, inhibits growth of cancer cells in culture and in vivo by causing apoptosis but the sequence of events leading to cell death is poorly defined. Here, we demonstrate that DATS-induced apoptosis in LNCaP human prostate cancer cells is initiated by reactive oxygen species (ROS) and regulated by Bax/Bak and X-linked inhibitor of apoptosis (XIAP) proteins. The DATS-mediated apoptosis in LNCaP cells was accompanied by mitochondrial swelling (revealed by transmission electron microscopy), disruption of mitochondrial membrane potential (revealed by flow cytometry after staining the cells with membrane potential sensitive dye JC-1), and cytosolic release of apoptogenic molecules (revealed by immunofluorescence microscopy for cytochrome c and Smac/DIABLO). The DATS-induced cell death in LNCaP cells correlated with induction of Bax and Bak, mitochondrial translocation (activation) of Bax, and a decrease in protein levels of Bcl-2 and Bcl-xL. The SV40 immortalized mouse embryonic fibroblasts (MEFs) derived from Bax and/or Bak knockout mice, but not Bid knockout mice, were significantly more resistant to DATS-induced apoptosis compared with the MEFs derived from wild-type mice. Moreover, combined knockdown of Bax and Bak proteins using siRNA conferred statistically significant protection against DATS-induced apoptosis in LNCaP cells. On the other hand, ectopic expression of either Bcl-2 or Bcl-xL in LNCaP cells did not have any appreciable effect on the cell death caused by DATS. The DATS treatment caused a marked decrease in protein levels of XIAP in LNCaP cells, and the HCT116 derived XIAP-/- cells were relatively more sensitive to growth inhibition and apoptosis induction by DATS compared with wild-type HCT116 cells. The DATS treatment resulted in generation of ROS in LNCaP cells, which was attenuated by pretreatment with antioxidant N-acetylcysteine (NAC). The NAC pretreatment conferred near complete protection against DATS-mediated disruption of the mitochondrial membrane potential and apoptosis in LNCaP cells. The DATS-induced apoptosis was not affected by either p53 protein knockdown in LNCaP cells or overexpression of wild-type p53 in PC-3 cells. In conclusion, the present study reveals that the DATS-induced apoptosis is initiated by ROS and regulated by Bax/Bak and XIAP, but independent of Bcl-2, Bcl-xL, Bid and p53. This study was supported by NCI grant CA113363.
Abstract 15687: Early Repolarization and Implantable Cardioverter Defibrillator Events in Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)
Authors: Petsy P So, Brenda Gerull, Paul Angaran, Christian Steinberg, Adam Herman, Jean Champagne, Shubhayan Sanatani, Santabhanu Chakrabarti, Jeffrey S Healey, Vijay S Chauhan, David H Birnie, Raymond Yee, George J Klein, Matthew T Bennett, Richard Leather, Michael H Gollob, Christopher S Simpson, Mario Talajic, Martin Gardner, Andrew D Krahn
Journal: Circulation (2015)

Introduction: Early repolarization (ER) has been implicated as a rare primary arrhythmic disorder, and a more common cofactor is arrhythmia risk. Our objective was to determine if ER is associated with increased implantable cardioverter defibrillator (ICD) events in patients with unexplained cardiac arrest and their first degree relatives (FDR). Methods: The cardiac arrest survivors with preserved ejection fraction registry (CASPER) is a national registry that systematically examines unexplained cardiac arrest probands and their FDR. The presence of ER was identified in serial ECGs. ER was defined as J-point elevation ≥ 0.1 mV above the isoelectric line in ≥ 2 contiguous inferior (II, III, avF) or lateral leads (I, avL, V4-V6), excluding V1-V3. ICD event rates, including appropriate ICD shocks and anti-tachycardia pacing (ATP) and mortality were assessed. Results: One hundred and seventy-nine subjects from 13 Canadian sites were studied (age 46±17 years, 89 males). Overall, 99/104 (95%) probands and 6/75 (8%) FDR received an ICD. Eighty-eight probands and 3 FDR had at least one follow-up visit. After 4 ± 2 years of follow-up, 15 probands had appropriate ICD shock (17%), 13 had ATP (15%) and 22 had either (25%). A total of 566 ECGs were analyzed for ER (3 ± 2 ECGs/subject). Twenty-nine of the 88 probands had ER (33%), and 6 had appropriate ICD shock (21%), 5 had ATP (17%) and 9 had either (31%). For those who had ER, Cox regression demonstrated trends towards a higher risk of first ICD shock or ATP (HR=1.9, 95% CI 0.76-4.73, p=0.17), first ICD shock (HR =2.1, 95% CI 0.81-5.17, p=0.13) and first ATP (HR=1.6, 95% CI 0.49-5.32, p=0.42). ATP was seen in 1 FDR and none had ICD shock. For those who had an ICD event and ER, a diagnosis was obtained in 5/9 patients: ER syndrome in 1, long QT syndrome in 3 and mitral annular ventricular tachycardia in 1. The remaining 4 had idiopathic ventricular fibrillation. One proband died after 3.2 years of follow-up with a confirmed diagnosis of sarcoidosis without ER. Conclusion: ER may be associated with a higher risk of recurrent ICD events in apparently unexplained cardiac arrest patients, especially if the underlying etiology is presumed electrical rather than structural.
A Hyperdynamic RV Is an Early Marker of Clinical Decompensation and Cardiac Recovery in Aortic Stenosis With Normal LV Ejection Fraction
Authors: Marzia Rigolli, Sanjay Sivalokanathan, Sacha Bull, Rohan S. Wijesurendra, Rina Ariga, Margaret Loudon, Jane M. Francis, Theodoros D. Karamitsos, Stefan Neubauer, Masliza Mahmod, Saul G. Myerson
Journal: JACC. Cardiovascular imaging (2018)
Altered cancer metabolism in mechanisms of immunotherapy resistance
Authors: Rishab Ramapriyan, Mauricio S. Caetano, Hampartsoum B. Barsoumian, Ana Carolina P. Mafra, Erika Pereira Zambalde, Hari Menon, Efrosini Tsouko, James W. Welsh, Maria Angelica Cortez
Journal: Pharmacology & Therapeutics (2018)
Multidrug-resistant Neisseria gonorrhoeae isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018
Authors: Daniel Golparian, Lisa Rose, Almida Lynam, Aia Mohamed, Beatrice Bercot, Makoto Ohnishi, Brendan Crowley, Magnus Unemo
Journal: Eurosurveillance (2018)

We describe a multidrug-resistant Neisseria gonorrhoeae urethritis case with ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual man in Ireland, August 2018. Whole-genome sequencing showed that the isolate IR72 belongs to the internationally spreading multidrug-resistant ceftriaxone-resistant FC428 clade, initially described in Japan in 2015. IR72 was assigned MSLT ST1903, NG-MAST ST17842 and NG-STAR type 1133, including the ceftriaxone resistance-mediating penA- 60.001. Global awareness of spreading ceftriaxone-resistant gonococcal strains that threaten recommended dual therapies is essential.
Abstract 18192: Electrical and Morphologic Characteristics of the Left Atrial Appendage Remnant After an Incomplete Exclusion Using Lariat Device
Authors: Dhanunjaya Lakkireddy, Rizwan Afzal, Donita Atkins, Mohit Turagam, Matthew Earnest, Randall Lee, Luigi Di Biase, Andrea Natale, Nitish Badhwar, Abdi Rasekh, Jie Cheng
Journal: Circulation (2016)

Background: Left atrial appendage (LAA) is incompletely excluded in some patients after a Lariat ligation. We describe the electrical and mechanical characteristics of these left atrial appendage r...
Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment
Authors: Silke Kern, Jeremy A. Syrjanen, Kaj Blennow, Henrik Zetterberg, Ingmar Skoog, Margda Waern, Clinton E. Hagen, Argonde C. van Harten, David S. Knopman, Clifford R. Jack, Ronald C. Petersen, Michelle M. Mielke
Journal: JAMA Neurology (2018)

<h3>Importance</h3> Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau). <h3>Objective</h3> To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations. <h3>Design, Setting and Participants</h3> The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid. <h3>Main Outcomes and Measures</h3> Risk of MCI. <h3>Results</h3> At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI. <h3>Conclusions and Relevance</h3> Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid.
Treatment with Combination of Dabrafenib and Trametinib in Patients with Recurrent/Refractory BRAF V600E-Mutated Hairy Cell Leukemia (HCL)
Authors: Robert J. Kreitman, Philippe Moreau, Martin Hutchings, Anas Gazzah, Jean-Yves Blay, Zev A. Wainberg, Alexander Stein, Sascha Dietrich, Maja J.A. de Jonge, Wolfgang Willenbacher, Jacques De Greve, Evgeny Arons, Farhad Ravandi, Fatima Rangwala, Paul Burgess, Bijoyesh Mookerjee, Vivek Subbiah
Journal: Blood (2018)
AB0646 Identification of risk factors for recurrence in polymyalgia rheumatica
Authors: A. Ueno, M. Hirata, Y. Yamamura, K. Fujita, N. Shibutou, M. Yamamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Glucocorticoids (GCs) are effective for polymyalgia rheumatica (PMR); however, some patients relapse during GC tapering and develop adverse events of GCs. <h3>Objectives</h3> To identify risk factors for recurrence in patients with polymyalgia Rheumatica(PMR). <h3>Methods</h3> Cox proportional hazards regression analyses was performed 78 patients with PMR who had been treated by 2015 EULAR/ACR recommendations between January2015 and December 2017 in our centre. The following data at baseline were collected retrospectively: age, sex, time of diagnosis, location of arthralgia/myalgia, maximum dose of prednisolone, US findings of shoulder, laboratory data before the initial treatment. <h3>Results</h3> Seventy-eight patients had been diagnosed with the 2012 EULAR/ACR provisional classification criteria for PMR, and had been treated first with GCs. They were at the age of 71.7±9.5, including 34 males and 44 females. Duration of symptoms before therapy was 2.0±2.0 months and the PMR duration was 21.2±15.5 months. Twenty-seven patients had arthralgia/myalgia other than shoulders and hips. The maximum dose of prednisolone was 15.9±4.4 mg/day. US findings of shoulder were positive in 65 patients. Relapses occurred in 37 patients (47%), when the dose of prednisolone was reduced to 5.6±5.5 mg/day at 8.9±6.4 months. MTX (8.6±3.1 mg/wk) was added in 29 patients or the dose of prednisolone was increased in 8 patients, similarly to the 2015 EULAR/ACR recommendations for the management of PMR. Additional MTX was ineffective in 16 patients, followed by adding tocilizumab in 8 patients. Forty patients discontinued GCs at 17.6±10.6 months. On univariate analysis, 4 variables were identified as significant risk factors affecting PMR recurrence: increased platelets (p=0.00192), low IgA (p=0.00149), arthralgia/myalgia limited to shoulders and hips (p=0.02), and the maximum dose of prednisolone used (p=0.0062). These 4 variables were introduced into the multivariate analysis, and the following 3 variables were retained as independent significant risk factors: the maximum dose of prednisolone(p&lt;0.005), limitation of arthralgia/myalgia to shoulders and hips(p&lt;0.05) and low IgA (p&lt;0.005). <h3>Conclusions</h3> These results indicate that the maximum dose of prednisolone, the absence of peripheral joint pains and low IgA may be associated with the recurrence in PMR patients <h3>Disclosure of Interest</h3> None declared
Abstract P013: Elevated Resting Heart Rate in Mid-Life is Associated With Cognitive Change Over 20-years: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Stephanie Z Wang, Oluwaseun E Fashanu, Di Zhao, Eliseo Guallar, Rebecca F Gottesman, Andrea L Schneider, John W McEvoy, Faye L Norby, Alvaro Alonso, Amer I Aladin, Erin D Michos
Journal: Circulation (2018)

Background: Resting heart rate (RHR) is an easily measured marker that is independently associated with cardiovascular disease (CVD) risk. There are several potential mechanisms by which RHR could affect cognitive function, but little is known about the relation of RHR and cognitive decline. We examined the association of RHR with 20 year cognitive decline in a community-based cohort. Methods: We studied 13,720 middle-aged white and black participants without a prior history of stroke or atrial fibrillation. RHR was obtained from a 12-lead resting electrocardiogram at baseline (1990-1992). Cognitive testing was measured at baseline and at up to two additional visits (1996-1998 and 2011-2013). A 3-test combined cognitive score was summed from these tests: delayed word recall, digit symbol substitution and word fluency. RHR was categorized into groups as &lt; 60 (reference), 60-69, 70-79 and ≥80 bpm. We examined the association of RHR with cognitive decline using linear mixed-effects models adjusted for demographic, socioeconomic, CVD risk factors, and AV nodal blockade use. ApoE genotype was included as a possible predictor. Imputation methods were used to account for attrition over follow-up. Results: Mean (SD) age of participants at baseline was 58 (6) years; 56% were women, 24% black. Average (SD) RHR was 66 (10) bpm, with RHR distribution: &lt;60 (28%), 60-69 (40%), 70-79 (23%), &gt;80 (9%) bpm. Over a mean follow-up of 20 years, participants in each RHR group exhibited cognitive decline (Table Part A). However, there was relatively greater global cognitive decline for those with RHR 70-79 and &gt;80 bpm compared to &lt;60 bpm (Part B). Results were consistent when excluding participants on AV nodal blockade medications. Conclusion: Elevated RHR is independently associated with greater cognitive decline over 20 years. Further studies are needed to determine whether the association is causal or secondary to another underlying process. If causal, future studies can determine whether modification of RHR can reduce cognitive decline.
Abstract 13133: The Association of Coronary Artery Calcification (CAC) With Subsequent Cardiovascular Disease (CVD) in DCCT/EDIC
Authors: Matthew J Budoff, Jye-Yu C Backlund, David A Bluemke, Joseph Polak, Ionut Bebu, David Schade, Suzanne Strowig, Philip Raskin, John M Lachin
Journal: Circulation (2018)

Introduction: The coronary artery calcium (CAC)-score has been validated to improve risk assessments for future cardiovascular events in general populations; however, this association has not been ...
Mechanisms of radiation enhancement by the CHK1 inhibitor PF-477736
Authors: Carleen Cullinane, Jeanette Raleigh, Kenna Anderes, Grant McArthur
Journal: Cancer Research (2007)

5386  CHK1 kinase is a key regulator of the S and G2 cell cycle checkpoints that are activated in response to DNA damage. Cell cycle arrest upon DNA damage checkpoint activation facilitates DNA repair thereby maintaining genomic integrity. Inhibition of CHK1 abrogates DNA damage induced cell cycle arrest and sensitizes cells to DNA damaging agents in vitro. The aim of this study was to investigate the effect of inhibition of CHK1 on the cellular response of A431 cells to ionizing radiation (IR) in vitro and in vivo using a novel small molecule CHK1 inhibitor, PF-477736. In vitro studies were performed to investigate the effects of PF477736 on clonogenic survival and cell cycle parameters following IR. Treatment of A431 cells with PF-477736 resulted in radiosensitization as indicated by reduced clonogenic survival following IR. Exposure of A431 cells to 10 Gy IR resulted in G2 arrest. In contrast, PF-477736 treatment of cells induced a marked reduction in IR-induced G2 arrest consistent with abrogation of the G2 checkpoint. This was further supported by a marked increase in PF-477736 treated cells entering mitosis after IR as detected by phospho-histone H3 staining (4.5 % vs 0.8 % at 10 hr post IR). Mice bearing A431 subcutaneous tumors were treated with 5 daily 3Gy radiation fractions alone or in combination with PF-477736. Compared to controls the observed tumor growth delay for radiation alone was 2.9 days and 6.7 days for radiation plus PF-477736. The radiation and PF-477736 combination showed enhanced antitumor efficacy with a 2.7 enhancement ratio compared to radiation alone. To define the role of p53 in the cellular response to CHK1 inhibition following IR, the HCT116 cell line and its isogenic p53-/- variant were used. Clonogenic survival assays revealed that PF-477736 enhanced the cytotoxic effects of radiation in both cell lines (parental: P = 0.001; p53-/- P = 0.002). Cell cycle analysis showed HCT116 cells accumulated in G1 and G2 at 24 hr following IR. Cells irradiated in the presence of PF-477736 however progressed through mitosis and accumulated in G1 consistent with the abrogation of the G2 checkpoint and the presence of a functional G1 checkpoint in this line. In distinct contrast, HCT116 p53-/- cells arrested in G2/M with 4N DNA content following IR and PF-477736 treatment. The effect of PF-477736 on IR-induced DNA damage and apoptosis in these cells will be presented. Clonogenic survival assays also revealed enhanced sensitivity of the p53-/-, but not the parental cells to PF-477736 in the absence of IR at drug doses known to inhibit CHK1 activation.
Methods of Screening for Cervical Cancer
Authors: George Yizhou Tang, Jay Parekh
Journal: JAMA (2018)

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
High plasma FGF21 levels predicts major cardiovascular events in patients treated with atorvastatin (from the Treating to New Targets [TNT] Study)
Authors: Kwok Leung Ong, Nicholas Hui, Andrzej S. Januszewski, Nadeem O. Kaakoush, Aimin Xu, Rana Fayyad, David A. DeMicco, Alicia J. Jenkins, Anthony C. Keech, David D. Waters, Philip J. Barter, Kerry-Anne Rye
Journal: Metabolism (2018)
Fungal propagules in house dust. I.
Authors: A. P. Verhoeff, E. S. van Reenen‐Hoekstra, R. A. Samson, P. J. Brunekreef, J. H. van Wijnen
Journal: Allergy (1994)

The presence of viable mold propagules in house dust was investigated by 10 different analytic methods, in order to determine to what extent different results are obtained when different analytic methods are used. Moreover, the value of this measurement as an estimator of the potential exposure to fungi in epidemiologic studies was assessed. Floor and mattress dust was sampled in 60 homes in The Netherlands during autumn 1990. For investigation of the variability in time, sampling was repeated in 20 homes after 6 weeks. Each analytic method is characterized by a unique combination of culture medium, suspension medium, and dilution step. The highest mean number of colony‐forming units (CFU)/g dust was obtained by suspension of at least 100 mg dust in a peptone or sucrose solution in a ratio of 1:50 (w/w), followed by 10‐fold dilution and plating on DG18 agar (geometric mean (GM) approximately 60000 CFU/g dust). The lowest mean number of CFU/g dust was obtained by direct plating of 30 mg dust on V8 agar (GM approximately 5300 CFU/g dust). The mean coefficient of variation of duplicate analyses varied from 11%, for suspension in sucrose and plating on DG18 agar, to 27%, for suspension and dilution in sucrose in combination with V8 agar. The highest mean number of species isolated was obtained by direct plating of 30 mg dust on DG18 agar (mean number of species: 17). Suspension and dilution on DG18 or V8 agars yielded an average of approximately six species. In duplicate analyses, the mean percentage of agreement for the species isolated varied from approximately 35%, for suspension and dilution, to 60%, for direct plating. The reproducibility of the number of CFU/g dust in time was better for mattress dust than for floor dust; however, also for mattress dust, the predictive value of a single measurement was rather low. The variability in time in species isolated was substantial, both for mattress dust and floor dust. We concluded that results of measurements of viable mold propagules in house dust, both quantitatively and qualitatively, depend greatly on the analytic methods used. Furthermore, a single measurement of fungal propagules in settled house dust does not provide a reliable measure of potential exposure to fungi in indoor environments.
Stereotactic body radiotherapy (SBRT) versus conventional fractionated intensity-modulated radiotherapy (CF-IMRT) for Asian patients with early-stage localized prostate cancer: Acute toxicity results from a prospective randomized phase II study
Authors: D.M. Poon, D. Lam, K. Wong, F. Mok, F. Mo, C.M. Chu, A.C.F. Ng, J. Suen, A.T.C. Chan
Journal: Annals of Oncology (2018)