tbuckley/cabot-search huggingface dataset:
Radioresistant Cancer Cells Can Be Conditioned to Enter Senescence by mTOR Inhibition
Authors: Hae Yun Nam, Myung Woul Han, Hyo Won Chang, Yoon Sun Lee, Myungjin Lee, Hyang Ju Lee, Byoung Wook Lee, Hee Jin Lee, Kyung Eun Lee, Min Kyo Jung, Hyesung Jeon, Seung-Ho Choi, Neung Hwa Park, Sang Yoon Kim, Seong Who Kim
Journal: Cancer Research (2013)

Autophagy is frequently activated in radioresistant cancer cells where it provides a cell survival strategy. The mTOR inhibitor rapamycin activates autophagy but paradoxically it also enhances radiosensitivity. In this study, we investigated the mechanisms of these opposing actions in radiation-resistant glioma or parotid carcinoma cells. Radiation treatment transiently enhanced autophagic flux for a period of 72 hours in these cells and treatment with rapamycin or the mTOR inhibitor PP242 potentiated this effect. However, these treatments also increased heterochromatin formation, irreversible growth arrest, and premature senescence, as defined by expression of senescence-associated β-galactosidase activity. This augmentation in radiosensitivity seemed to result from a restoration in the activity of the tumor suppressor RB and a suppression of RB-mediated E2F target genes. In tumor xenografts, we showed that administering rapamycin delayed tumor regrowth after irradiation and increased senescence-associated β-galactosidase staining in the tumor. Our findings suggest that a potent and persistent activation of autophagy by mTOR inhibitors, even in cancer cells where autophagy is occurring, can trigger premature senescence as a method to restore radiosensitivity.
Evolving Insights About the Impact of Sensory Deficits in the Elderly
Authors: Patrick G. O’Malley
Journal: JAMA Internal Medicine (2013)

Frank R. Lin, MD, PhD; Kristine Yaffe, MD; Jin Xia, MS; Qian-Li Xue, PhD; Tamara B. Harris, MD, MS; Elizabeth Purchase-Helzner, PhD; Suzanne Satterfield, MD, DrPH; Hilsa N. Ayonayon, PhD; Luigi Ferrucci, MD, PhD; Eleanor M. Simonsick, PhD; for the Health ABC Study Group
Fruits, Vegetables, and Colon Cancer Risk in a Pooled Analysis of 14 Cohort Studies
Authors: A. Koushik, D. J. Hunter, D. Spiegelman, W. L. Beeson, P. A. van den Brandt, J. E. Buring, E. E. Calle, E. Cho, G. E. Fraser, J. L. Freudenheim, C. S. Fuchs, E. L. Giovannucci, R. A. Goldbohm, L. Harnack, D. R. Jacobs, I. Kato, V. Krogh, S. C. Larsson, M. F. Leitzmann, J. R. Marshall, M. L. McCullough, A. B. Miller, P. Pietinen, T. E. Rohan, A. Schatzkin, S. Sieri, M. J. Virtanen, A. Wolk, A. Zeleniuch-Jacquotte, S. M. Zhang, S. A. Smith-Warner
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundFruit and vegetable intakes have been associated with a reduced risk of colon cancer; however, in more recent studies associations have been less consistent. Statistical power to examine associations by colon site has been limited in previous studies.
Etanercept plus ciclosporin versus etanercept plus methotrexate for maintaining clinical control over psoriatic arthritis: a randomised pilot study
Authors: Fabiola Atzeni, Laura Boccassini, Marco Antivalle, Fausto Salaffi, Piercarlo Sarzi-Puttini
Journal: Annals of the Rheumatic Diseases (2010)

Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8<sup>+</sup> T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-αβ, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system.
Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis
Authors: J. Bowes, G. Orozco, E. Flynn, P. Ho, R. Brier, H. Marzo-Ortega, L. Coates, R. McManus, A. W. Ryan, D. Kane, E. Korendowych, N. McHugh, O. FitzGerald, J. Packham, A. W. Morgan, I. N. Bruce, A. Barton
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To investigate a shared genetic aetiology for skin involvement in psoriasis and psoriatic arthritis (PsA) by genotyping single-nucleotide polymorphisms (SNPs), reported to be associated in genome-wide association studies of psoriasis, in patients with PsA. <h3>Methods</h3> SNPs with reported evidence for association with psoriasis were genotyped in a PsA case and control collection from the UK and Ireland. Genotype and allele frequencies were compared between PsA cases and controls using the Armitage test for trend. <h3>Results</h3> Seven SNPs mapping to the IL1RN, TNIP1, TNFAIP3, TSC1, IL23A, SMARCA4 and RNF114 genes were successfully genotyped. The IL23A and TNIP1 genes showed convincing evidence for association (rs2066808, p = 9.1×10<sup>−7</sup>; rs17728338, p = 3.5×10<sup>−5</sup>, respectively) whilst SNPs mapping to the TNFAIP3, TSC1 and RNF114 genes showed nominal evidence for association (rs610604, p = 0.03; rs1076160, p = 0.03; rs495337, p = 0.0025). No evidence for association with IL1RN or SMARCA4 was found but the power to detect association was low. <h3>Conclusions</h3> SNPs mapping to previously reported psoriasis loci show evidence for association to PSA, thus supporting the hypothesis that the genetic aetiology of skin involvement is the same in both PsA and psoriasis.
NHS's main regulator has lost public confidence, say MPs
Authors: A. O'Dowd
Journal: BMJ (2013)

The NHS’s main regulator, the Care Quality Commission (CQC), has lost the confidence of the public and will have to work hard to regain trust, MPs have claimed.

MPs on the parliamentary health select committee have also warned that the ongoing registration of general practices by the commission will be a major challenge and a test of whether the regulator has learnt from past mistakes.

MPs on the committee published a critical report on 9 January,1 resulting from its annual accountability hearing in September last year,2 which focused on the commission.

The new report says that despite sustained criticism over a prolonged period and several scandals over standards of healthcare the commission has not yet successfully defined its core purpose or earned public confidence.

The MPs conclude that the commission’s main focus should be to ensure …
A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the eastern cooperative oncology group study E2200
Authors: B.J. Giantonio, D.E. Levy, P.J. O'Dwyer, N.J. Meropol, P.J. Catalano, A.B. Benson
Journal: Annals of Oncology (2006)
Is iron over-rated? Sulphates may be the more important compound in development of colitis in rodent models, and perhaps humans
Authors: Alan L Buchman
Journal: Gut (2011)

<h3>Abstract</h3> Electron microscopy (EM) volume reconstruction is a powerful tool for investigating the fundamental structure of brain circuits, but the full potential of this technique is limited by the difficulty of integrating molecular information. High quality ultrastructural preservation is necessary for EM reconstruction, and intact, highly contrasted cell membranes are essential for following small neuronal processes through serial sections. Unfortunately, the antibody labeling methods used to identify most endogenous molecules result in compromised morphology, especially of membranes. Cryofixation can produce superior morphological preservation and has the additional advantage of allowing indefinite storage of valuable samples. We have developed a method based on cryofixation that allows sensitive immunolabeling of endogenous molecules, preserves excellent ultrastructure, and is compatible with high-contrast staining for serial EM reconstruction.
Free-Floating Thrombi in the Right Heart
Authors: Ludovic Chartier, Jérôme Béra, Maxence Delomez, Philippe Asseman, Jean-Paul Beregi, Jean-Jacques Bauchart, Henri Warembourg, Claude Théry
Journal: Circulation (1999)

Floating right heart thrombi (FRHTS) are a rare phenomenon, encountered almost exclusively in patients with suspected or proven pulmonary embolism and diagnosed by transthoracic echocardiography. Their management remains controversial.We report on a series of 38 consecutive patients encountered over the past 12 years. Thirty-two patients were in NYHA class IV, 20 in cardiogenic shock. Echocardiography usually demonstrated signs of cor pulmonale: right ventricular overload (91.7% of the population), paradoxical interventricular septal motion (75%), and pulmonary hypertension (86. 1%). The thrombus was typically wormlike (36 of 38 patients). It extended from the left atrium through a patent foramen ovale in 4 patients. Pulmonary embolism was confirmed in all but 1. Mortality was high (17 of 38 patients) irrespective of the therapeutic option chosen: surgery (8 of 17), thrombolytics (2 of 9), heparin (5 of 8), or interventional percutaneous techniques (2 of 4). The in-hospital mortality rate was significantly linked with the occurrence of cardiac arrest. Conversely, the outcome after discharge was usually good, because 18 of 21 patients were still alive 47.2 months later (range, 1 to 70 months).Severe pulmonary embolism was the rule in our series of FRHTS (mortality rate, 44.7%). The choice of therapy had no effect on mortality. Emergency surgery is usually advocated. However, thrombolysis is a faster, readily available treatment and seems promising either as the only treatment or as a bridge to surgery. In patients with contraindications to surgery or lytic therapy, interventional techniques may be proposed.
Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review
Authors: R. Le Scodan, F. Mornex, N. Girard, C. Mercier, P.-J. Valette, M. Ychou, F. Bibeau, P. Roy, J.-Y. Scoazec, C. Partensky
Journal: Annals of Oncology (2009)
Early-Stage Hodgkin's Lymphoma: In Pursuit of Perfection
Authors: Anas Younes
Journal: Journal of Clinical Oncology (2012)

It was estimated that 8,830 patients would be diagnosed with Hodgkin’s lymphoma (HL) in the United States in 2011, and that approximately half of those patients would have early-stage disease. The treatmentofearly-stageHLhasevolvedovertime,resultingincontinuous improvement in the cure rate and reductions in treatment-related toxicity. Today, combined modality programs are considered the standard of care for the majority of these patients, with an expected cure rate exceeding 80% and survival rate exceeding 90%. Despite these outstanding results, several groups continue to develop treatment programs in the hopes of achieving better curative and safety outcomes. To understand the results of key randomized studies in patients with early-stage HL, it is important to remember that the definition of early-stage disease varies widely among study groups and in different regions of the world. In North America, early stage is defined as stage I or II disease with no bulk or B symptoms. Patients with such disease are typically treated with four cycles of doxorubicin, bleomycin, dacarbazine, and vinblastine (ABVD) plus 30 Gy of involved field radiation therapy (IF-XRT). In contrast, patients with bulky disease ( 10 cm) are usually grouped with patients with advanced-stage disease and are treated with six to eight cycles of ABVD plus 36 Gy of IF-XRT, resulting in a 5-year failure-free survival of 85% and an overall survival of 95%. The definition of early stage that is used by the German Hodgkin’s Lymphoma Study Group (GHLSG) includes bulky stage I or II disease with no B symptoms. The GHLSG additionally classifies patients with early-stage disease into favorable (stage I/II disease with no risk factors such as bulk, elevated erythrocyte sedimentation rate, extranodal sites, or more than two involved lymph node regions) or unfavorable (stage I/II with any of these risk factors) categories. Patients with early-stage favorable HL have an excellent cure rate; therefore, investigations of new therapeutic programs focus on reducing treatment-related toxicity, whereas patients with early-stage unfavorable HL continue to be candidates for the evaluation of new regimens that are aimed at additionally improving the cure rate. Using this approach, the GHLSG reported that patients with early-stage favorable HL could be successfully treated with a reduced-intensity regimen of two cycles of ABVD chemotherapy plus 20 Gy of IF-XRT instead of the standard four cycles of ABVD plus 30 Gy of IF-XRT. Using such a strategy, they were able to maintain a high 91% rate of freedom from treatment failure. In the article that accompanies this editorial, the GHLSG reports the results of the HD14 study that was aimed at improving treatment outcomes of patients with early-stage unfavorable HL by intensifying
A Model for Primary Care Delivery to a Widely Dispersed Medically Indigent Population
Authors: Victoria Bigelow
Journal: JAMA (1991)

Access to Care is a unique program uniting private and public resources to provide primary care to the uninsured poor. The model was designed to serve a medically indigent population that is dispersed over a large geographic area, where clinics are not a practical option. Care for illness is provided in the offices of private physicians throughout the area and supported by laboratory, radiology, and pharmacy services. The program is designed for the estimated 88,000 persons in suburban Cook County, Illinois, with family incomes of less than twice the federal poverty level, who are uninsured and ineligible for Medicaid and Medicare. Supported by grants from foundations and local governments, the program, which has been in operation for 2 years in two demonstration areas, is administered by a private not-for-profit confederation of four health and social service organizations.
Epidemiology of patients diagnosed with influenza A admitted to the Universitary La Paz Hospital (HULP) in the periods 2009-2010 and 2011-2012
Authors: M. Concepcion Prados, Sandra Rojas, Ana Martinez-Virto, Rodolfo Lvarez-Sala, Ana Santiago, Antonia Gómez-Mendieta, Antonio Martinez-Verdasco, Jaime Fernández-Bujarrabal, Sergio Alcolea, Yolanda Martinez-Abad
Journal: European Respiratory Journal (2013)

AIM 

It was to describe the epidemiology characteristics of patients with Influenza A admitted in the periods of 2009-2010 and 2011-2012

PATIENTS/METHOD 

This descriptive study included all patients diagnosed with influenza A by PCR who were admitted in the Pulmonology service, HULP in July 2009-February 2010 (group 1) and in December 2011-February 2012 (group 2). Data were analyzed using SAS 9.1, using the chi-square test, Fisher exact test, Student t-test and the Mann-Whitney. Confidenciality was mantained.

RESULTS 

We included 121 patients diagnosed with Influenza A, (71% group 1) and (29% group 2) (54% male). The median age: 49.2 + / - 21.8 (15-95) years. 59% had some risk factors: chronic lung (27%), cardiovascular (21.5%), metabolic (16%) and immunodeficiency (15%) diseases. The most common complication was pneumonia (45%), 48% in group 1 and 37% in group 2. 4% required admission to the ICU, (mean days 8.4 + / - 8.3). 97.5% has received oseltamivir for 4.8 days. Comparing the two periods, it was found that there were differences in terms of age and risk factors

View this table:

Table 1





No differences in others variables were found. 100% were treated with Oseltamivir in Group 1 and 91% in group 2. 4 patients died, all in the period of 2011-2012.

CONCLUSIONS 

Comparing the epidemiological characteristics of patients hospitalized with influenza A in both periods of time, we can say that the seasonal flu affects older patients with more risk factors caused by the H3N2.
The Kaposi’s Sarcoma-Associated Herpesvirus (KSHV/HHV-8) K1 Protein Induces Expression of Angiogenic and Invasion Factors
Authors: Ling Wang, Naohiro Wakisaka, Christine C Tomlinson, Scott M DeWire, Stuart Krall, Joseph S Pagano, Blossom Damania
Journal: Cancer Research (2004)

Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) has been linked to Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. In addition to endothelial cells and B lymphocytes, KSHV also has been shown to infect epithelial cells and keratinocytes. The transmembrane glycoprotein K1, encoded by the first open reading frame of KSHV, is a signaling protein capable of eliciting B-cell activation. We show that KSHV K1 can induce expression and secretion of vascular endothelial growth factor (VEGF) in epithelial and endothelial cells. Up-regulation of VEGF was mediated at the transcriptional level because expression of K1 resulted in VEGF promoter activation. We also show that K1 induces expression of matrix metalloproteinase-9 (MMP-9) in endothelial cells. Additional analyses with K1 mutant proteins revealed that the SH2 binding motifs present in the K1 cytoplasmic tail are necessary for VEGF secretion and MMP-9 induction. These results indicate that K1 signaling may contribute to KSHV-associated pathogenesis through a paracrine mechanism by promoting the secretion of VEGF and MMP-9 into the surrounding matrix.
Adenosine stimulates nitric oxide synthesis in vascular smooth muscle cells
Authors: U Ikeda
Journal: Cardiovascular Research (1997)

Objective: The aim was to investigate the effects of adenosine on nitric oxide (NO) synthesis in vascular smooth muscle cells. Methods: NO and cAMP synthesis was measured in confluent rat vascular smooth muscle cells in culture at passage 5–10, using Griess reagent and an enzyme immunoassay kit, respectively. The expression of inducible NO synthase mRNA was assayed by Northern blotting. Results: Incubation of cultures with interleukin-1β (10 ng/ml) for 24 h caused a significant increase in nitrite production. The interleukin-1β-induced nitrite production by vascular smooth muscle cells was significantly increased by adenosine or its stable analogue, 2-chloroadenosine, in a dose-dependent manner. The adenosine A2a receptor antagonist, KF17837, but not the A1 receptor antagonist, DPCPX, significantly inhibited 2-chloroadenosine-mediated nitrite production. The 2-chloroadenosine-induced nitrite production by interleukin-1β-stimulated cells was accompanied by increased inducible NO synthase mRNA accumulation. In the presence of dibutyryl-cAMP (1 mM), interleukin-1β-induced nitrite accumulation was further increased, but the effect of 2-chloroadenosine was not additive or synergistic. Addition of 2-chloroadenosine dose-dependently increased intracellular cAMP levels of vascular smooth muscle cells. Conclusions: These results indicate that adenosine acts on A2 receptors and augments NO synthesis in interleukin-1β-stimulated vascular smooth muscle cells, at least partially through a cAMP-dependent pathway.
Therapy of acute hepatitis C
Authors: Alfredo Alberti, Silvia Boccato, Alessandro Vario, Luisa Benvegnù
Journal: Hepatology (2002)

Acute hepatitis C has a high propensity to become chronic, which provides the rationale for treating patients with acute disease attempting to prevent chronicity. Almost all published studies on therapy of acute hepatitis C have been small in size, uncontrolled, and highly heterogeneous as to patient features, dose and duration of treatment, follow-up evaluation, and criteria used to define efficacy and safety. The published studies on treatment of acute hepatitis C have used standard alfa or beta interferon monotherapy: none have evaluated combination therapy of interferon and ribavirin or peginterferon. Several meta-analyses of published studies have concluded that initiation of interferon monotherapy during the acute phase of hepatitis C virus (HCV) infection significantly reduces (by 30% to 40%) evolution to chronic hepatitis. The tolerability of interferon in acute hepatitis C has been excellent, even in symptomatic and icteric patients; the side effects and adverse events being similar in type and frequency to those seen when treating chronic cases. Thus, currently available data support treatment of patients with acute hepatitis C, but data are insufficient to draw firm conclusions about which patients to treat, when therapy should be started, or what regimen is optimal. Future studies of adequate size and design should focus on efficacy and tolerability of peginterferons and whether therapy should be started immediately after diagnosis or delayed for 2 to 4 months to avoid treatment of patients who spontaneously recover.
Acetaminophen may act through endorphin
Authors: H Sprott
Journal: Annals of the Rheumatic Diseases (2005)

Acetaminophen, also known as paracetamol, is a non-steroidal anti-inflammatory drug (NSAID) with potent antipyretic and analgesic actions but with very weak anti-inflammatory activity. The mechanism of action of acetaminophen is still not clearly understood. It has no known endogenous high affinity binding sites. In addition, acetaminophen does not appear to share with …
Degradation of connective tissue components by lung derived leucocytes in vitro: role of proteases and oxidants.
Authors: G M Brown, K Donaldson
Journal: Thorax (1988)

Inflammatory leucocytes are implicated in connective tissue damage during chronic inflammatory lung disease. In an investigation of the role of leucocytes in connective tissue derangements in the lung, inflammatory leucocytes were generated in rat lungs by intratracheal instillation of inflammatory agents and retrieved by bronchoalveolar lavage. The proteolytic activities of control macrophages and of two inflammatory cell populations were compared; iodinated collagen, laminin, and fibronectin matrices were used. The inflammatory cells caused consistently and substantially more degradation of the matrices than the controls on a per cell basis. The oxidant scavengers superoxide dismutase and catalase did not inhibit matrix degradation, but alpha 1 protease inhibitor and alpha 2 macroglobulin were inhibitory. It is concluded that matrix damage in this assay is enhanced by inflammatory cells and is mediated principally by serine protease activity.
Comparison of Central Corneal Thickness Measurements by Rotating Scheimpflug Camera, Ultrasonic Pachymetry, and Scanning-Slit Corneal Topography
Authors: Shiro Amano, Norihiko Honda, Yuki Amano, Satoru Yamagami, Takashi Miyai, Tomokazu Samejima, Miyuki Ogata, Kazunori Miyata
Journal: Ophthalmology (2006)
Collagenous colitis associated with small intestinal villous atrophy.
Authors: I Hamilton, S Sanders, D Hopwood, I A Bouchier
Journal: Gut (1986)

Two patients diagnosed as having small intestinal hyperplastic villous atrophy and being treated with a gluten free diet were investigated because of persistent watery diarrhoea. Both were found to have collagenous colitis. Previous reports of this condition have emphasised the presence of normal small intestinal mucosal architecture and the association of collagenous colitis with intestinal villous atrophy has not previously been reported. Both cases responded to oral steroid therapy, but not to other previously recommended treatment regimens.