tbuckley/cabot-search huggingface dataset:
Phosphodiesterase 2 Mediates Redox-Sensitive Endothelial Cell Proliferation and Angiogenesis by Thrombin via Rac1 and NADPH Oxidase 2
Authors: Isabel Diebold, Talija Djordjevic, Andreas Petry, Armin Hatzelmann, Hermann Tenor, John Hess, Agnes Görlach
Journal: Circulation Research (2009)

Cyclic nucleotide phosphodiesterases (PDEs) control the levels of the second messengers cAMP and cGMP in many cell types including endothelial cells. Although PDE2 has the unique property to be activated by cGMP but to hydrolyze cAMP, its role in endothelial function is only poorly understood. Reactive oxygen species (ROS) have been recognized as signaling molecules controlling many endothelial functions. We thus investigated whether PDE2 would link to ROS generation and proliferative responses in human umbilical vein endothelial cells in response to thrombin. Thrombin stimulated the GTPase Rac1, known to activate NADPH oxidases, and enhanced ROS formation, whereas PDE2 inhibition or depletion by short hairpin (sh)RNA prevented these responses. Similar observations were made with 8-Br-cGMP or atrial natriuretic peptide. In agreement, thrombin elevated cGMP but decreased cAMP levels, whereas db-cAMP or forskolin diminished Rac1 activity and ROS production. Subsequently, PDE2 overexpression activated Rac1, increased ROS generation, and enhanced proliferation and in vitro capillary formation. These responses were not observed in the presence of inactive Rac1 or shRNA against the NADPH oxidase subunit NOX2. Inhibition or depletion of PDE2 also prevented thrombin-induced proliferation and capillary formation. Importantly, downregulation of PDE2 by lentiviral shRNA or PDE2 inhibition prevented vessel sprouting from mouse aortic explants and in vivo angiogenesis in a mouse model, respectively. In summary, PDE2 promotes activation of NADPH oxidase-dependent ROS production and subsequent endothelial proliferation and angiogenesis. Targeting PDE2 may provide a new therapeutic approach in diseases associated with endothelial dysfunction, oxidative stress, vascular proliferation, and angiogenesis.
Online Quality Control, Hyperfractionated Radiotherapy Alone and Reduced Boost Volume for Standard Risk Medulloblastoma: Long-Term Results of MSFOP 98
Authors: Christian Carrie, Jacques Grill, Dominique Figarella-Branger, Valerie Bernier, Laetitia Padovani, Jean Louis Habrand, Mohamed Benhassel, Martine Mege, Marc Mahé, Philippe Quetin, Jean Philippe Maire, Marie Helene Baron, Pierre Clavere, Sophie Chapet, Philippe Maingon, Claire Alapetite, Line Claude, Anne Laprie, Sophie Dussart
Journal: Journal of Clinical Oncology (2009)

To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance.Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Société Française d'Oncologie Pédiatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales.After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, -1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline.HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.
Serum KL-6 level as a monitoring marker in a patient with pulmonary alveolar proteinosis
Authors: M. Nakajima, T. Manabe, Y. Niki, T. Matsushima
Journal: Thorax (1998)

A raised serum level of KL-6 is known to exist in active pulmonary fibrosis and KL-6 may be produced and secreted by type II pneumocytes. A case is described of pulmonary alveolar proteinosis with high serum KL-6 levels. The serum KL-6 level decreased after whole lung washing and correlated with symptoms, opacities on the chest radiograph, and arterial blood gas measurements. The serum KL-6 level may represent a useful marker for pulmonary alveolar proteinosis.
The Incubation of Scarlet Fever
Authors: W. T. Smith
Journal: BMJ (1883)

and a cracked-pot sound.Phthisical bacilli were present in the sputum.He also suffered from ana.l fistula.His weight, on December 19th, 122 lbs. 4 ozs.; on the 30th, 124 lbs. 8ozs.REMARKS.-In this case the cough was much benefited.CASE vII.-JuliaN
A Guide for Drug Use in Depressive Disorders
Authors: ALLEN RASKIN
Journal: American Journal of Psychiatry (1974)

The author extracts information from the multihospital NIMH collaborative studies of drugs and depression that might be of practical use to the clinician. The drugs used in these controlled studies were chlorpromazine, imipramine, diazepam, and phenelzine, drugs that exert different effects on the major symptoms of depression and on certain patient subtypes. The author also describes the frequency and nature of adverse reactions to these drugs.
GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function
Authors: Sara Mostafavi, Debajyoti Ray, David Warde-Farley, Chris Grouios, Quaid Morris
Journal: Genome biology (2008)

Abstract Background: Most successful computational approaches for protein function prediction integrate multiple genomics and proteomics data sources to make inferences about the function of unknown proteins. The most accurate of these algorithms have long running times, making them unsuitable for real-time protein function prediction in large genomes. As a result, the predictions of these algorithms are stored in static databases that can easily become outdated. We propose a new algorithm, GeneMANIA, that is as accurate as the leading methods, while capable of predicting protein function in real-time. Results: We use a fast heuristic algorithm, derived from ridge regression, to integrate multiple functional association networks and predict gene function from a single process-specific network using label propagation. Our algorithm is efficient enough to be deployed on a modern webserver and is as accurate as, or more so than, the leading methods on the MouseFunc I benchmark and a new yeast function prediction benchmark; it is robust to redundant and irrelevant data and requires, on average, less than ten seconds of computation time on tasks from these benchmarks. Conclusion: GeneMANIA is fast enough to predict gene function on-the-fly while achieving state-of-the-art accuracy. A prototype version of a GeneMANIA-based webserver is available at http://morrislab.med.utoronto.ca/prototype .
Is aspirin for colorectal cancer prevention on the prime time yet?
Authors: Joseph JY Sung
Journal: Gut (2014)

Aspirin is the most widely studied drug for chemoprevention of colorectal cancer but there are limitations. First the risk-benefit issue has not been fully addressed. What is the risk of bleeding associated with prescribing aspirin to asymptomatic individuals versus the benefit of cancer protection one can obtain from this treatment? Second, the optimal dosing, frequency and duration of aspirin usage in average-risk subjects (ie, patients with non-cardiovascular disease and patients with non-familial polyposis) have not been settled. Third, the potential ethnic difference has not been studied. Up to now, almost all studies were conducted in the Western population. Would Asians be responding to the treatment equally well?

There are new and important data to support the use of aspirin in preventing colorectal cancer (CRC). Rothwell et al recently published their long-term data in 20-year follow-up studies giving strong support to the use of low-dose aspirin (75–300 mg daily) in cancer prevention.1 ,2 These data which pool from five important randomised studies examine the effects of primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA trial, Dutch TIA trial) included over 14 000 patients with a median follow-up of more than 18 years. The long-term use of aspirin resulted in significant reduction of colon cancer incidence …
Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration
Authors: Colby Chiang, Jessie C Jacobsen, Carl Ernst, Carrie Hanscom, Adrian Heilbut, Ian Blumenthal, Ryan E Mills, Andrew Kirby, Amelia M Lindgren, Skye R Rudiger, Clive J McLaughlan, C Simon Bawden, Suzanne J Reid, Richard L M Faull, Russell G Snell, Ira M Hall, Yiping Shen, Toshiro K Ohsumi, Mark L Borowsky, Mark J Daly, Charles Lee, Cynthia C Morton, Marcy E MacDonald, James F Gusella, Michael E Talkowski
Journal: Nature Genetics (2012)
Nucleic Acid Recognition by the Innate Immune System
Authors: Roman Barbalat, Sarah E. Ewald, Maria L. Mouchess, Gregory M. Barton
Journal: Annual Review of Immunology (2011)

Receptors of the innate immune system recognize conserved microbial features and provide key signals that initiate immune responses. Multiple transmembrane and cytosolic receptors have evolved to recognize RNA and DNA, including members of the Toll-like receptor and RIG-I-like receptor families and several DNA sensors. This strategy enables recognition of a broad range of pathogens; however, in some cases, this benefit is weighed against the cost of potential self recognition. Recognition of self nucleic acids by the innate immune system contributes to the pathology associated with several autoimmune or autoinflammatory diseases. In this review, we highlight our current understanding of nucleic acid sensing by innate immune receptors and discuss the regulatory mechanisms that normally prevent inappropriate responses to self.
Insulin Resistance, β-Cell Dysfunction, and Conversion to Type 2 Diabetes in a Multiethnic Population
Authors: Carlos Lorenzo, Lynne E. Wagenknecht, Ralph B. D'Agostino, Marian J. Rewers, Andrew J. Karter, Steven M. Haffner
Journal: Diabetes Care (2009)

Insulin resistance and beta-cell function are major predictors of type 2 diabetes, but studies using direct methods of insulin resistance and secretion are few and relatively small. Furthermore, the strength of these associations has not been tested in different ethnic groups and various states of glucose tolerance, family history of diabetes, and obesity.Predictors of incident diabetes were evaluated in Hispanic, non-Hispanic white, and African American participants in the Insulin Resistance Atherosclerosis Study (aged 40-69 years). In 557 participants with normal glucose tolerance and 269 with impaired glucose tolerance (IGT), insulin sensitivity (insulin sensitivity index [S(I)]) and first-phase insulin secretion (acute insulin response [AIR]) were directly measured using the frequently sampled intravenous glucose tolerance test.At the 5-year follow-up examination, 128 (15.5%) individuals had developed diabetes. Both S(I) (odds ratio x 1 SD 0.50 [95% CI 0.37-0.68]) and AIR (0.51 [0.40-0.65]) were independent predictors of incident diabetes even after adjustment for age, sex, ethnicity, center, IGT, family history of diabetes, and BMI. The strength of the relation of S(I) and AIR to incident diabetes was not significantly affected by potential interactions of age, sex, ethnicity, glucose tolerance, BMI, or family history of diabetes (P > or = 0.15).Both insulin sensitivity and beta-cell function predict conversion to diabetes in different ethnic groups and various states of glucose tolerance, family history of diabetes, and obesity. The prevention of type 2 diabetes should focus on interventions that improve both insulin resistance and insulin secretion.
Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anaemia
Authors: T. Steinmetz, B. Tschechne, O. Harlin, B. Klement, M. Franzem, J. Wamhoff, H. Tesch, R. Rohrberg, N. Marschner
Journal: Annals of Oncology (2012)

Intravenous (i.v.) iron can improve anaemia of chronic disease and response to erythropoiesis-stimulating agents (ESAs), but data on its use in practice and without ESAs are limited. This study evaluated effectiveness and tolerability of ferric carboxymaltose (FCM) in routine treatment of anaemic cancer patients.
<i>ARID1A</i> Mutations in Cancer: Another Epigenetic Tumor Suppressor?
Authors: Jennifer N. Wu, Charles W.M. Roberts
Journal: Cancer Discovery (2012)

Although disordered chromatin organization has long been recognized as a feature of cancer, the molecular underpinnings of chromatin structure, epigenetic regulation, and their relationships to transcription are only beginning to be understood. Cancer genome sequencing studies have revealed a novel theme: frequent mutation of epigenetic regulators. Among these, the ARID1A/BAF250A subunit of the SWI/SNF (BRG1-associated factors) chromatin remodeling complex has emerged as recurrently mutated in a broad array of tumor types. We review the genomic and functional data supporting classification of ARID1A as a tumor suppressor.Mutations in chromatin remodeling complex genes are increasingly recognized in many cancer types. However, the mechanisms by which chromatin remodeling complexes contribute to gene expression and the cancer phenotype are poorly understood. Understanding how mutation of chromatin remodelers facilitates transformation may offer the potential for development and implementation of novel therapies for cancer.
Dye-marking and fiducial marker placement via conventional and electromagnetic navigation bronchoscopy (ENB): New interdisciplinary approach to suspicious intrapulmonary nodules
Authors: Lars Hagmeyer, Ulrike Oesterlee, Martin Kocher, Burkhart Schilcher, Dirk Wassenberg, Wilfried Budach, Christina Priegnitz, Winfried Randerath
Journal: European Respiratory Journal (2013)

Background: Conventional and electromagnetic navigation bronchoscopy (ENB) is used in diagnostic approach to suspicious pulmonary nodules. Using these techniques to perform fiducial marker placement and dye-marking of lesions can be an innovative approach enabling risk reduced therapy.  Materials und Methods: We present 4 cases where conventional bronchoscopy and ENB were used in an experimental interdisciplinary approach for therapy planning. We analyzed indications, endoscopic procedures and post-interventional outcome.  Results: In one female patient (history of cervix carcinoma), ENB was used to mark a 2 mm subpleural nodule. The dye-marked pleural spot enabled the surgeon to perform a parenchyma-sparing wedge resection via VATS. The pathological findings showed malignancy.  In two male patients (NSCLC), surgery and conventional stereotactic radiotherapy was impossible due to end-stage COPD. ENB was used for fiducial marker placement prior to cyberknife radiotherapy. No procedure related complications were observed. Partial remission could be achieved without post-radiation-fibrosis.  In one male patient, a peripheral endoluminal relapse was diagnosed following a right upper lobe resection for a NSCLC. The tumor could not be clearly identified by computertomography, so that bronchoscopic placement of a fiducial marker was performed in order to allow stereotactic radiotherapy.  Conclusion: Dye-Marking and fiducial marker placement is a new bronchoscopic techniques for an interdisciplinary approach to suspicious lesions. In the described cases therapy planning was successful, no complications were observed.
Differential gene expression profiling of adult murine hematopoietic stem cells
Authors: In-Kyung Park, Yaqin He, Fangming Lin, Ole D. Laerum, Qiang Tian, Roger Bumgarner, Christopher A. Klug, Kaijun Li, Christian Kuhr, Michelle J. Doyle, Tao Xie, Michèl Schummer, Yu Sun, Adam Goldsmith, Michael F. Clarke, Irving L. Weissman, Leroy Hood, Linheng Li
Journal: Blood (2002)
UnTEThering (Smooth Muscle) Cell Plasticity
Authors: Domenick A. Prosdocimo, Rajan Jain, Mukesh K. Jain
Journal: Circulation (2013)

C ellular plasticity has become the subject of intense research, with perhaps the greatest example provided by the recent Nobel Prize winners Drs Yamananka and Gurdon and the demonstration that terminally differentiated fibroblasts can be coaxed into assuming an embryonic stem celllike fate.Emerging evidence suggests that plasticity inherent in cells may be hijacked in the progression of disease and cancer.However, the mechanisms by which cells acquire and regulate this plasticity remain incompletely understood.It is appreciated that broad programs must be unleashed during these switches, and, therefore, control at the epigenetic level in regulating these processes has garnered significant interest.In this issue of Circulation, Liu et al 1 provide evidence implicating the epigenetic factor termed ten-eleven translocation-2 (TET2) in control of vascular smooth muscle cell (VSMC) plasticity and development of vascular disease.
Motherese by any other name: Mother-infant communication in non-hominin mammals
Authors: John D. Newman
Journal: Behavioral and Brain Sciences (2004)

The definition of motherese is extended to infant-directed vocalizations in non-hominin mammals. In many species, vocal interactions between mothers and their infants are common. The neural substrates mediating these interactions include the rostral limbic cortex of the frontal lobe. Spoken language may have arisen from hominin females vocalizing to their infants.
Detection of Breast Cancer With Addition of Annual Screening Ultrasound or a Single Screening MRI to Mammography in Women With Elevated Breast Cancer Risk
Authors: Wendie A. Berg, Zheng Zhang, Daniel Lehrer, Roberta A. Jong, Etta D. Pisano, Richard G. Barr, Marcela Böhm-Vélez, Mary C. Mahoney, W. Phil Evans, Linda H. Larsen, Marilyn J. Morton, Ellen B. Mendelson, Dione M. Farria, Jean B. Cormack, Helga S. Marques, Amanda Adams, Nolin M. Yeh, Glenna Gabrielli
Journal: JAMA (2012)

IX PREVIOUS SINGLE-CENTERstudies [1][2][3][4][5][6] and 3 multicenter trials 7-9 have shown supplemental screening breast ultrasound significantly increases detection of node-negative invasive breast cancer in women with mammographically dense breast tissue on the first prevalence screen, consistently increasing cancer detection (yield) by 3.5 per 1000 in single-center studies and from 4.2 to 4.4 per 1000 in multicenter trials.The vast majority of cancers detected only by ultrasound have been node-negative invasive breast cancers.Until now, it was See also p 1379.
Estrogen replacement therapy, atherosclerosis, and vascular function
Authors: T Mikkola
Journal: Cardiovascular Research (2002)

There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (>65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women or monkeys in the early stages of atherosclerosis progression has marked beneficial effects. Whether progestogens attenuate the cardiovascular benefits of estrogen replacement therapy has been controversial for more than a decade. Current evidence from studies of both monkeys and women suggest little or no attenuation of estrogen benefits for coronary artery atherosclerosis. Lack of compliance with estrogen replacement therapy, usually because of fear of breast cancer, remains a major problem. Future regimens may overcome that fear by the co-administration of a breast cancer preventive agent (i.e., selective estrogen receptor modulators, phytoestrogens) with low dose estrogen.
The Withdrawal of Drugs for Commercial Reasons
Authors: Vinay Prasad
Journal: JAMA Internal Medicine (2014)

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Nitric Oxide/cAMP Interactions in the Control of Rat Renal Vascular Resistance
Authors: Peter Sandner, Mark Kornfeld, Xiaoping Ruan, William J. Arendshorst, Armin Kurtz
Journal: Circulation Research (1999)

Abstract —This study aimed to characterize the interaction between nitric oxide (NO)- and cAMP-related pathways in the control of renal blood flow. Using the isolated perfused rat kidney model, we determined the effects of inhibition of NO formation by N ω -nitro- l -arginine methyl ester (L-NAME; 1 mmol/L) and of NO administration by sodium nitroprusside (SNP, 10 μmol/L) on renal vascular resistance under conditions of elevated vascular cAMP levels. cAMP levels were increased either by adenylate cyclase activation via isoproterenol or by inhibition of cAMP phosphodiesterases (PDEs) 1, 3, and 4. We found that L-NAME markedly increased vascular resistance and that this effect was completely reversed by SNP. Both isoproterenol and inhibitors of the cAMP PDEs lowered basal vascular resistance. In the presence of isoproterenol (3 nmol/L) and inhibitors of PDE-1 [8-methoxymethyl-l-methyl-3-(2-methylpropyl)-xanthine; 8-MM-IBMX, 20 μmol/L] and PDE-4 (rolipram, 20 μmol/L), L-NAME again substantially increased vascular resistance, and this effect of L-NAME was completely reversed by SNP. In the presence of the PDE-3 inhibitors milrinone (20 μmol/L) and trequinsin (200 nmol/L), however, both L-NAME and SNP failed to exert any additional effects. Because PDE-3 is a cGMP-inhibited cAMP PDE and because the vasodilatory effect of SNP was abrogated by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (20 μmol/L), our findings are compatible with the idea that an action of NO on PDE-3 could account for the vasodilatory properties of NO on the renal vasculature. Moreover, our findings suggest that PDE-3 activity is an important determinant of renal vascular resistance.