tbuckley/cabot-search huggingface dataset:
Chelation of iron enhances invasion of glioblastoma cells
Authors: Anja Elstner, Nikola Holtkamp, Andreas von Deimling
Journal: Cancer Research (2007)

3086  Diffusely infiltrating malignant cells, one of the hallmarks of glioblastoma multiforme (GBM, WHO IV), cannot efficiently be reached by surgical resection, radio- and chemotherapy. The prognosis for patients affected with GBM is poor. Understanding the mechanisms of the invasive behavior will contribute to improved treatment. Previous results of our group pointed towards the involvement of the iron pathway in the invasiveness of rat glioma cells.  In this study we examined the effect of the iron chelator desferrioxamine (DFO). Intracellular iron depletion in human GBM-cell lines DBTRG05MG and U373MG was achieved by application of DFO. Invasion of cells was examined by Transwell-infiltration assays. Expression of invasion associated factors was analyzed with Western Blot and Fluorescence Activated Cell Sorting.  We detected induction of GBM invasion after treatment of cells with 50 µM DFO. This was accompanied by an induction of expression of urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinase type 2 playing a major role in degradation of extracellular matrix and GBM-invasion. Inhibition with topotecan demonstrated that hypoxia inducible factor 1 alpha was involved in DFO-induced uPAR expression. Inhibition of uPAR with siRNA resulted in reduced DFO-mediated GBM-invasion.  Our results hint towards a problem of an anti-proliferative therapy with iron chelators in invasive tumors such as GBM. The anti-proliferative effect of iron depletion comes at the cost of enhanced invasion.
Antisocial personality disorder and HIV infection among intravenous drug abusers
Authors: R K Brooner, L Greenfield, C W Schmidt, G E Bigelow
Journal: American Journal of Psychiatry (1993)

Antisocial personality disorder in drug abusers has been associated with poor treatment outcome. The authors examined the relationship between diagnosis of antisocial personality and HIV infection.Subjects were 272 intravenous drug abusers, 140 (52%) of whom were in methadone treatment. Subjects were given an HIV risk behavior interview before diagnostic interviewing and HIV testing.Using the DSM-III-R definition, the authors found that 119 (44%) of the subjects met criteria for antisocial personality. Significantly more of the subjects with antisocial personality (18% [N = 21] than of the subjects without antisocial personality (8% [N = 12]) had HIV infection. The diagnosis of antisocial personality disorder was associated with a significantly higher odds ratio of infection independent of ethnicity, gender, and treatment status.Antisocial personality is a risk factor for HIV infection among intravenous drug abusers.
Abstract 16507: Decreased Annular Dynamic Motion in Ischemic Mitral Regurgitation: Implication for Annuloplasty Selection
Authors: Melissa M Levack, Arminder S Jassar, Benjamin M Jackson, Thomas J Eperjesi, Stuart J Weiss, Albert T Cheung, Jeremy D Kukafka, Joseph H Gorman, Robert C Gorman
Journal: Circulation (2011)

Introduction: There is consensus that mitral valve repair procedures for ischemic mitral regurgitation (IMR) should employ undersized annuloplasty rings to restore normal annular area. Some surgeon...
Plasma cortisol secretion and REM period latency in adult endogenous depression
Authors: G M Asnis, U Halbreich, E J Sachar, R S Nathan, L C Ostrow, H Novacenko, M Davis, J Endicott, J Puig-Antich
Journal: American Journal of Psychiatry (1983)

The authors studied the relationship of plasma cortisol secretion and REM period latency in 25 patients with endogenous depression. The 8 patients (32%) with cortisol hypersecretion had a significantly shortened REM period latency in comparison with the 17 with normal cortisol secretion. Furthermore, an extremely short REM latency (20 minutes or less) occurred almost exclusively in those with cortisol hypersecretion. The authors discuss possible neurotransmitter disturbances responsible for these abnormalities and the clinical implications of these findings.
Abstract 15238: The Impact of Aspirin, Beta-Blockers, Statins(T3), and Angiotensin Converting Enzyme-Inhibitors(ACE-I) for the Reduction of Perioperative and Long-Term Mortality in High Risk Patients Undergoing Major Vascular Surgery
Authors: Wei C Lau, James B Froehlich, Daniel G Montgomery, Theresa Shields, Peter K Henke, Kim A Eagle
Journal: Circulation (2011)

Background: A combination of beta-blockers and statins independently reduced perioperative mortality and nonfatal myocardial infarction (MI) in patients undergoing vascular surgery. This study exam...
A 15-Year Warranty Period for Asymptomatic Individuals Without Coronary Artery Calcium
Authors: Valentina Valenti, Bríain ó Hartaigh, Ran Heo, Iksung Cho, Joshua Schulman-Marcus, Heidi Gransar, Quynh A. Truong, Leslee J. Shaw, Joseph Knapper, Anita A. Kelkar, Pratik Sandesara, Fay Y. Lin, Sebastiano Sciarretta, Hyuk-Jae Chang, Tracy Q. Callister, James K. Min
Journal: JACC. Cardiovascular imaging (2015)
Abstract 13472: NT-proBNP is Prognostic for Stroke and Death in Atrial Fibrillation - a RELY Substudy
Authors: Ziad Hijazi, Jonas Oldgren, Ulrika Andersson, Stuart J Connolly, Michael D Ezekowitz, Paul A Reilly, Agneta Siegbahn, Salim Yusuf, Lars Wallentin
Journal: Circulation (2010)

Background: Atrial fibrillation (AF) increases the risk of stroke and mortality. Natriuretic peptides are powerful prognostic biomarkers for mortality and cardiovascular (CV) events. The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its effect in addition to CHADS2 risk factors for predicting CV events in patients with AF has not been investigated previously. Methods: In the RELY study, 18113 patients (mean age 71 years) with AF and at least one risk factor for thromboembolism were randomized to dabigatran or warfarin and followed for 2.0 years median treatment duration. We analyzed plasma concentrations of NT-proBNP, Roche Diagnostics, at randomization in 6158 patients and evaluated its association to CV events after multivariable adjustment for CHADS2 risk factors and study drug. Reference levels for NT-proBNP were measured in 940 healthy subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of 71 year old men. Results: Median NT-proBNP...
Abstract 2779: Stress Single Photon Emission Computed Tomography Predicts Mortality in Asymptomatic Patients (without Chest Pain Syndrome) with Moderate Coronary Heart Disease Risk
Authors: Masud H Khandaker, Todd D Miller, Panithaya Chareonthaitawee, David O Hodge, Raymond J Gibbons
Journal: Circulation (2006)

Background The ACCF/ASNC Appropriateness Criteria Report categorizes single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) as an uncertain indication for both the de...
H32, a new non-quinone vitamin K sulfone analog, inhibits tumor cell growth by MAPK activation
Authors: Siddhartha Kar, Meifang Wang, Seung Wook Ham, Brian I. Carr
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3794 

We previously synthesized several K vitamin derivatives, which are potent growth inhibitors of human tumor cells, including Hep3B hepatoma cell line. Among these, Cpd 5 or [2-(2-mercaptoethanol)-3-mehyl-1,4-naphthoquinone] was the most potent (IC50= 6 μM). However, Cpd 5 is a quinone derivative and thus has the potential for generating toxic reactive oxygen species. We therefore synthesized a series of non-quinone sulfone analogs of vitamin K and compared their growth inhibitory activity on Hep3B cells. Among these, H32 was found to be the most potent (IC50= 5 μM). H32 also inhibited growth of several other human tumor cell lines, including melanoma and breast carcinoma. Interestingly, it was markedly less potent in inhibiting DNA synthesis of normal rat hepatocytes with an IC50 of 15 μM. The thiol-antioxidants glutathione and N-acetyl-L-cysteine antagonized H32-mediated growth inhibition, whereas the non-thiol-antioxidants catalase and superoxide dismutase did not. H32 preferentially inhibited the activity of the dual specific cell cycle phosphatase Cdc25A both in Hep3B hepatoma cells and in cell-free systems, likely by binding to the enzyme catalytic cysteine. It also induced prolonged phosphorylation of the MAPK proteins ERK1/2, JNK1/2 and p38. Furthermore, inhibitors of MAPK phosphorylation, including U0126, JNKI-II, and SB203580 antagonized H32-mediated growth inhibition. Cytosolic ERK phosphatase activity was inhibited by the action of H32. Thus, the non-quinone sufone vitamin K derivative H32 differentially inhibited growth of normal and neoplastic cells by inducing prolonged ERK phosphorylation, likely as a result of inhibition of cellular ERK phosphatase(s) action. This is an attractive model compound due to its selectivity of action and non-quinone nature.
An epidemiologic, clinical, and family study of simple schizophrenia in County Roscommon, Ireland
Authors: K S Kendler, M McGuire, A M Gruenberg, D Walsh
Journal: American Journal of Psychiatry (1994)

The authors sought to estimate the prevalence of simple schizophrenia, compare the clinical presentations and courses of simple and "typical" schizophrenia, and examine psychopathology in first-degree relatives of probands with simple schizophrenia, probands with typical schizophrenia, and community comparison subjects.The authors followed up all individuals with a recorded diagnosis of schizophrenia (N = 285) and 75% of those with a diagnosis of severe affective illness (N = 99) from the Roscommon County Case Register, which includes all individuals seeking psychiatric care in a rural county in western Ireland. The authors interviewed all available first-degree relatives of these groups and of matched unscreened community comparison subjects.Eleven cases of simple schizophrenia were diagnosed in the probands, for an estimated population prevalence and morbid risk in County Roscommon of 5.3 (SE = 1.6) and 6.2 (SE = 1.9) per 10,000, respectively. Individuals with typical schizophrenia (N = 126) had more marked delusions, hallucinations, and positive thought disorder; individuals with simple schizophrenia had more pronounced negative thought disorder and a more chronic course. Neither social/occupational functioning nor negative symptoms differed between the two groups. The risks for schizophrenia and all nonaffective psychoses were greater in the relatives of the probands with simple schizophrenia than in the relatives of the community comparison subjects.In this sample, simple schizophrenia was relatively rare, was rather debilitating, and resembled typical schizophrenia in presentation and course except for the absence of positive psychotic symptoms. From a familial perspective, simple schizophrenia appears to be related to typical schizophrenia.
Abstract 780: Atorvastatin Activates A Novel Nbs1-dependent Mechanism Of Accelerating Dna Repair In Atherosclerosis
Authors: Melli M Mahmoudi, Isabelle C Gorenne, John R Mercer, Nichola L Figg, Martin R Bennett
Journal: Circulation (2007)

There is increasing evidence that reactive oxidant species (ROS) and DNA damage promote the development and complications of atherosclerosis. Although statin therapy reduces both ROS and DNA damage in atherosclerosis, the mechanism of this effect is unknown. We first examined expression of DNA damage and repair markers in vascular smooth muscle cells (VSMCs) of human atherosclerotic plaques. With increasing disease severity, there was increased VSMC expression of the DNA repair markers P-ATM/ATR substrate and P-H2AX from 2.7%Â±2.2 and 0.5Â±0.71 [meanÂ±SEM] (AHA Grade I/II), to 21%Â±3.5 and 36.5Â±2.1 (Grade III) lesions, and 86.5%Â±0.7 and 69.3Â±7.6 (Grade IV/V). Cultured plaque VSMCs also showed a 1.5 fold increased oxidant stress; a 4.4 fold increased double-stranded DNA breaks, and expression of P-H2AX by Western blots. ROS analogues induced a robust DNA damage response in VSMCs, characterised by lengthening of tails on COMET assay, and activation of ATM and P-H2AX, with completion of repair by 6 hours. Atorvastatin pre-treatment accelerated DNA repair by approximately 2 hours without inhibiting ROS induction or DNA damage, and markedly accelerated the kinetics of nibrin (NBS-1) and P-H2AX activation, both proteins recruited to sites of DNA damage, by preventing degradation of NBS-1. Atorvastatin induced phosphorylation of HDM2, an E3 ligase and putative regulator of NBS-1 stability, and siRNA knockdown of HDM2 replicated the effect of atorvastatin on NBS-1. The ability of atorvastatin to accelerate repair was completely dependent upon NBS-1, as atorvastatin was ineffective in cells either null or expressing constitutively active NBS-I. In summary, we have demonstrated a novel NBS-1-dependent mechanism by which statins accelerate DNA repair in atherosclerosis, through HDM2 phosphorylation and stabilisation of NBS-1. We believe that both NBS-1 and HDM2 are critical to DNA repair in atherosclerosis.
Cytomegalovirus Drives Mixed Chimerism Following T-Cell Depleted Allogeneic HSCT, Providing Protective Immunity In The Absence Of GvHD
Authors: Rob S Sellar, Frederick Arce Vargas, Jake Henry, Simon Thomas, Alka Stansfield, Stephanie Verfuerth, Sarah C Charrot, Rachael E Hough, Sergio A Quezada, Kirsty J Thomson, Stephen Mackinnon, Karl S Peggs
Journal: Blood (2013)
Abstract 15604: Histopathologic Features of the Liver in Patients After Fontan Palliation
Authors: Fred M Wu, Maureen M Jonas, Gabriele Egidy Assenza, Michael J Landzberg, Anne Marie Valente, Chinweike Ukomadu, Antonio R Perez-Atayde
Journal: Circulation (2011)

BACKGROUND The Fontan procedure, a palliative operation for complex congenital heart disease, directs systemic venous blood into the pulmonary arteries without an intervening ventricle, resulting i...
Abstract A23: SMYD3 links methylation of MAP3K2 to Ras-driven tumors
Authors: Pawel K. Mazur, Nicolas Reynoird, Purvesh Khatri, Atul J. Butte, Alex Wilkinson, Benjamin Garcia, Shichong Liu, Michiel Vermeulen, Pascal W.T.C. Jansen, Peter J. Tummino, Ryan G. Kruger, Glenn S. Van Aller, Olena Barbash, Michael Huddleston, Or Gozani, Julien Sage
Journal: Cancer Research (2015)

Abstract The Ras family of oncogenes is activated in a large fraction of human cancers. Treatment of Ras-driven tumors with inhibitors of protein kinases in the Ras signaling network, such as Raf or MEK is a promising therapeutic strategy. However, toxicity issues and the emergence of tumor cells that are resistant to these drugs underscore the need for a better understanding of the Ras pathway and for the development of novel therapeutic options to improve the survival of cancer patients. Deregulation in lysine methylation signaling has emerged as a common etiologic factor in cancer pathogenesis, with inhibitors of several histone lysine methyltransferases (KMTs) being developed as chemotherapeutics. The largely cytoplasmic KMT SMYD3 (SET and MYND domain containing protein 3) is overexpressed in numerous human tumors. However, the molecular mechanism by which SMYD3 regulates cancer pathways and its relationship to tumorigenesis in vivo are largely unknown. Here we show that methylation of MAP3K2 by SMYD3 increases MAP Kinase signaling and promotes the formation of Ras-driven carcinomas. Using mouse models for pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LAC), we found that abrogating SMYD3 catalytic activity inhibits tumor development in response to oncogenic Ras. We employed protein array technology to identify the MAP3K2 kinase as a target of SMYD3. In cancer cell lines, SMYD3-mediated methylation of MAP3K2 at lysine 260 potentiates activation of the Ras/Raf/MEK/ERK signaling module. Finally, the PP2A phosphatase complex, a key negative regulator of the MAP Kinase pathway, binds to MAP3K2 and this interaction is blocked by methylation. Together, our results elucidate a new role for lysine methylation in integrating cytoplasmic kinase-signaling cascades and establish a pivotal role for SMYD3 in the regulation of oncogenic Ras signaling. Citation Format: Pawel K. Mazur, Nicolas Reynoird, Purvesh Khatri, Atul J. Butte, Alex Wilkinson, Benjamin Garcia, Shichong Liu, Michiel Vermeulen, Pascal W.T.C. Jansen, Peter J. Tummino, Ryan G. Kruger, Glenn S. Van Aller, Olena Barbash, Michael Huddleston, Or Gozani, Julien Sage. SMYD3 links methylation of MAP3K2 to Ras-driven tumors. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A23.
Abstract 28: KickinNutrition.TV: A Digital Nutrition Education Curriculum for Middle-School Students Increases Self-Efficacy for Healthy Habits.
Authors: Nicolette S Maggiolo, Raymond T Yan, Christine M Zakhour, Kaylie A Patrick, Tianjiao Cui, Paula A Quatromoni
Journal: Circulation (2015)

Child health promotion and obesity prevention efforts demand effective skills-based nutrition education. KickinNutrition.TV (KNTV) offers an innovation in school-based nutrition education where evidence-based curricula, teacher training, classroom time, and school resources are lacking. KNTV was designed using digital technology to empower students to get in the kitchen and cook by providing information and skills to increase consumption of fresh, whole foods. We assessed the hypothesis that exposure to KickinNutrition.TV would impact nutrition-related behaviors to a greater extent than exposure to traditional (non-digital) nutrition lessons. This quasi-experiment involved 1,105 students in 10 schools in three public school districts in Massachusetts (2 urban, 1 suburban). Schools were assigned in a 2:1 ratio within districts to receive either the digital KNTV curriculum or a comparison curriculum. Classroom teachers in each school were trained to deliver a set of 6 weekly nutrition lessons to students in 6th grade. Assessments included pre- and post-curriculum surveys of nutrition knowledge, personal behaviors, readiness to change and self-efficacy. Baseline surveys were completed by 1,052 (95%) students and 778 (82%) provided follow up surveys. The study sample was 51% female, 48% white, 26% Latino and 16.5% African American. At baseline, average nutrition knowledge scores were 69.8% ± 20% and were not different for students in KNTV or comparison classrooms. At baseline, about half of students (49%) reportedly ate vegetables on a daily basis and only 42% consumed milk or yogurt daily. Only 46% of students reported that they knew how to identify a whole grain food, with a similarly low percentage (47%) reportedly eating whole grain foods daily. One in three children reported being involved in helping to cook dinner for their family. At program conclusion, compared to students receiving traditional lessons, measurably larger shifts in self-efficacy were observed among students exposed to KNTV for being able to identify whole grain foods (p=.08) and for helping to cook dinner (p=.01). Larger shifts in readiness to change were observed among KNTV students for daily consumption of vegetables (p=.06) and breakfast (p=.03). About 40% of students increased their nutrition knowledge score but gains were not different by classroom type. Participation in KNTV was associated with greater likelihood of having eaten breakfast daily in the past week (p=.01) and for achieving My Plate guidelines for food variety at breakfast (p=.001) and lunch (p=.01). These data provide evidence of nutritional vulnerability among a diverse sample of middle-school students and demonstrate the positive impact of a novel nutrition education program. KickinNutrition.TV offers a digital solution to overcome several obstacles to nutrition education in schools.
Personalized Approach To Treatment of Acute Myeloid Leukemia Using a High-Throughput Chemosensitivity Assay
Authors: Ka Yee Yeung, C. Anthony Blau, Vivian G. Oehler, Su-In Lee, Christopher P. Miller, Sylvia Chien, Timothy Martins, Elihu H. Estey, Pamela S. Becker
Journal: Blood (2013)
Values, Myths, and Symbols
Authors: Rollo May
Journal: American Journal of Psychiatry (1975)

Defining "symbol" as that which draws together and unites experience and "myth" as a cluster of symbols set in dramatic form, the author discusses the lack of both symbols and myths in contemporary sociaty. This lack had led to a disintegration of commonly held values and, ultimately, to a great need for psychotherapy on the part of individuals seeking personal identity. The individual must define his or her own values according to personal myths. One basic function of psychotherapy is to help individuals in their attempt to recover values.
MDR1 gene expression and outcome in patients with osteosarcoma
Authors: A. F. Gharib, M. Abdel Kader, A. M. Morsy
Journal: Journal of Clinical Oncology (2008)

10544 Background: Increased expression of the multidrug resistance gene (MDR1) has been implicated in osteosarcoma prognosis. This study represents a prospective assessment of the prognostic value of MDR1 mRNA expression in patients with newly diagnosed extremity osteosarcoma. Methods: A series of 36 patients with high-grade, nonmetastatic osteosarcoma of the extremity were enrolled and observed prospectively for tumor recurrence. All patients were treated with pre- and postoperative chemotherapy and surgery. Preoperative chemotherapy consisted of two cycles of methotrexate (8 g/m2) plus leucovorin calcium (180 mg), cisplatin (120 mg/m2), and doxorubicin (60 mg/m2). Tumors from the thirty-six patients were analyzed for MDR1 mRNA expression Quantitative RT-PCR. The association of the level of MDR1 expression with the risk of systemic recurrence was examined using survival analyses with traditional and histologic markers as prognostic factors. Results: Using the highest MDR1 value for each patient, a dose-response relationship was not identified between the level of MDR1 expression and systemic relapse. In univariate analyses of the other prognostic factors, there was evidence that tumor size and necrosis ( 90% v > 90%) were associated with the risk of systemic relapse and weaker evidence that older patients were more likely to relapse. When all factors were considered in a multivariate model, only tumor size retained a significant relative risk. Conclusions: We did not identify any correlation between MDR1 mRNA expression and disease progression in patients with osteosarcoma. It is likely that alterations in other genes are involved in resistance to chemotherapy in osteosarcoma and that they play a more critical role than MDR1 in this disease. No significant financial relationships to disclose.
Abstract 14384: Cardiovascular Mortality In ESRD Patients Undergoing Coronary Artery Bypass Grafting Vs Percutaneous Coronary Intervention- A Meta Analysis
Authors: Arun Kannan, Saravanan Balamuthusamy, Mugilan Poongkunran, Vendhan Ramanujam, Raul Medina, Nagapradeep Nagajothi, Mark Borgstrom
Journal: Circulation (2013)