tbuckley/cabot-search huggingface dataset:
Abstract 2692: An ongoing Phase II trial of an adenovirus/PSA vaccine for prostate cancer
Authors: David M. Lubaroff, Richard D. Williams, Daniel Vaena, Fadi Joudi, James Brown, Mark Smith, Pamela Zehr, Erica Brown, Julie Eastman, Karen Griffith, Tammy Madsen, Kristine Johnson
Journal: Cancer Research (2012)

Abstract Introduction and Objectives: Our Phase I adenovirus/PSA vaccine trial has proved that this vaccine is safe. We are conducting a Phase II clinical trial with two separate protocols for patients with recurrent or hormone refractory prostate cancer assessing toxicity, immune responses, and changes in PSA levels. Methods: In Protocol #1 men with recurrent prostate cancer following definitive initial treatment for their disease were placed in one of two arms: Arm A; men receive the vaccine alone at days 0, 30, and 60; Arm B; men receive the vaccine 14 days after the initiation of androgen deprivation therapy (ADT). In Protocol #2 men with hormone refractory disease receive the vaccine alone using the same 3 injection schedule. Each injection consists of 108 pfu of the Ad/PSA vaccine suspended in a collagen matrix. All patients return at regular intervals for physical, chemical, radiologic, and immunologic evaluations. Results: To date forty four patients have been enrolled and have been followed a median of 12 months. The patients have a median age of 71.3 years, and median enrollment PSA levels of 0.62 ng/ml in Protocol #1 and 5.45 ng/ml in Protocol #2. In our preliminary results at this early stage of the trial, 100% of the patients in Protocol #1 and 67% of the patients in Protocol #2 demonstrated anti-PSA T cell responses above preinjection levels. Sixty four percent of the patients demonstrated an increase in PSA doubling time (PSADT). Conclusions: In an attempt to follow up on the success of our Phase I clinical trial of the Ad/PSA vaccine we have initiated a Phase II trial to investigate the therapeutic efficacy of the vaccine in men with recurrent prostate cancer, either following definitive therapy prior to other treatments or hormone refractory. Early results from the first four four patients demonstrate the induction of anti-PSA T cells responses in a high percentage of the vaccinated patients and increase in PSADT in more than half of the patients. No serious vaccine-related toxicities have been identified in the patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2692. doi:1538-7445.AM2012-2692
Incorporation of connexins into plasma membranes and gap junctions
Authors: P Martin
Journal: Cardiovascular Research (2004)

Gap junctions are polymeric assemblies of aligned pairs of interacting hexameric connexon hemichannel units facilitating direct intercellular communication. The principal process leading to assembly of gap junctions involves the cotranslational insertion of connexin (Cx) proteins into the endoplasmic reticulum, followed by their rapid oligomeric association into homo- or heteromeric connexons that are trafficked via the Golgi apparatus to the plasma membrane. Oligomerisation is a high-fidelity process that determines connexon channel stoichiometry and conductance characteristics. A large number of mutations in Cx26 and Cx32 detected in genetic diseases have emphasised the requirement for precise oligomerisation of connexins into hexameric connexons that traffic to the plasma membrane. Mutations in Cx43 are rare, and in the cardiovascular system, where it is the dominant connexin, disease changes are linked to its abundance and to gap junction remodelling. Connexins with short carboxyl tails may also be post-translationally inserted as oligomeric channels directly into plasma membranes. This mechanism of channel assembly is highly dependent on microtubule integrity and may allow cells to rapidly modulate gap junctional cross talk.
Imminent brain death: point of departure for potential heart-beating organ donor recognition
Authors: Yorick J. de Groot, Nichon E. Jansen, Jan Bakker, Michael A. Kuiper, Stan Aerdts, Andrew I. R. Maas, Eelco F. M. Wijdicks, Hendrik A. van Leiden, Andries J. Hoitsma, Berry Kremer, Erwin J. O. Kompanje
Journal: Intensive Care Medicine (2010)

There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E0M0B0R0. The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.
RETRACTED ARTICLE: Asiaticoside, a trisaccaride triterpene induces biochemical and molecular variations in brain of mice with parkinsonism
Authors: Uvarajan Sampath, Vanisree Arambakkam Janardhanam
Journal: Translational Neurodegeneration (2013)

Abstract Background Parkinson’s disease characterized by oxidative stress and mitochondrial damage in the pars compacta of substantia nigra remains a challenge to manage with an added disadvantage of side effects of L-levo dopa, the standard drug used for therapy. Thus, an alternative approach of utilizing natural components would be beneficial in the management of the disease. The present study was aimed to investigate the potential role of asiaticoside (As), a trisaccaride triterpene against1 – methyl 4 – phenyl 1,2,3,6 tetrahydropyridine (MPTP)-induced neurotoxicity in experimental mice. Methods Mice were divided into 4 groups: Group I received vehicle saline, group II was treated with 20 mg/kg of body weight of MPTP (2 doses with 2 h intervals), group III received MPTP along with 50 mg/kg body weight of As for the 21 consecutive days starting from the day of MPTP intoxication. Group IV received 50 mg/kg body weight of asiaticoside for the same period serving as drug control. Animals were sacrificed at the end of experimental period and the striatum and midbrain samples were analyzed for enzyme assays, transmission electron microscopic (TEM) analysis. Immunofluorescent assay was performed to study the expression of GFAP to detect astrocyte, which are activated due to neuronal damage. Imunohistochemical studies were carried out to quantify the expression of Bax and Bcl2, the molecular signatures that would provide clues of the extent of neurodegeneration. Results The activities of enzymes were increased on As administration when compared with those of group II animals. Expressions of Bax and Bcl2 along with GFAP did show significant variations (p &lt; 0.05) on MPTP treatment when compared to control animals and the changes were found to be reversed significantly (p &lt; 0.05) after treatment with asiaticoside. TEM analysis also showed attenuated degenerative architecture on As administration. The mice which received As alone (drug control IV) did not show significant variation from that of the control mice. Conclusion The observations suggest that asiaticoside may be efficacious in protecting neurons from the oxidative damage caused by the insult of MPTP.
Anal and Rectal Diseases Explained
Authors: A Emmanuel
Journal: Gut (2004)

E D Ehrenpreis. London: Remedica, 2003, £20.00, pp 215. ISBN 1 901346 67 6

Eli Ehrenpreis, a respected senior North American physician, has completed the latest volume in a series of “ Explained ” mini textbooks. The series is intended as a source of concise information for physicians. The content is comprehensive, including subjects often missed by physicians and surgeons alike, such as sexually transmitted …
UN High-Level Meeting on Non-Communicable Diseases: addressing four questions
Authors: Robert Beaglehole, Ruth Bonita, George Alleyne, Richard Horton, Liming Li, Paul Lincoln, Jean Claude Mbanya, Martin McKee, Rob Moodie, Sania Nishtar, Peter Piot, K Srinath Reddy, David Stuckler
Journal: The Lancet (2011)
PTU-185 Update On The Halt-it Trial Progress: Tranexamic Acid For The Treatment Of Gastrointestinal Haemorrhage – An International, Randomised, Double Blind Placebo Controlled Trial
Authors: V Jairath, H Shakur, P Edwards, K Ker, D Manno, I Gilmore, A Veitch, S Stanworth, T Coats, I Roberts
Journal: Gut (2014)

<h3>Introduction</h3> Gastrointestinal (GI) bleeding is a common medical emergency and an important cause of morbidity and mortality in high, middle and low income countries. Despite advances in resuscitative, pharmacological and endoscopic therapy, re-bleeding occurs in 10% of patients with non-variceal bleeding and up to 25% of those with variceal bleeding and is an important predictor of death. Excessive fibrinolysis may play an important role both in the failure to control initial bleeding and in the precipitation of re-bleeding through premature breakdown of blood clots at sites of vascular injury. This raises the possibility that an antifibrinolytic drug administered following GI bleeding could limit severity of bleeding and transfusion requirements. <h3>Methods</h3> HALT-IT has been designed as a large, pragmatic randomised controlled trial which aims to quantify the efficacy and safety of tranexamic acid (TXA) in adults with significant acute upper or lower gastrointestinal bleeding. The trial will determine the effect of early administration of TXA on mortality, morbidity, blood transfusion, surgical intervention and health status in patients with GI bleeding. The primary outcome is death in hospital within 28 days of randomisation. Secondary outcomes include re-bleeding, need for surgery or radiological intervention, blood product transfusion and thromboembolic events. <h3>Results</h3> UK recruitment began in August 2013. By January 2014, a total of 507 patients were randomised across 26 actively recruiting sites, averaging a recruitment rate of 20 patients per week. Centralised and statistical data monitoring ensures trial participants meet inclusion criteria and allows real time monitoring of event rates for the primary and secondary outcomes. The results will be presented by intention to treat and a pre-specified subgroup analysis will also determine the treatment effect in patients with liver cirrhosis and variceal bleeding. <h3>Conclusion</h3> HALT-IT aims to recruit 8000 participants in hospitals worldwide and recruitment is ahead of schedule based upon a strong performance in the UK. The success of the trial to date has been dependent upon multi-disciplinary and societal engagement as well as infrastructural support provided by NIHR research networks. The results will add to our expanding knowledge about the role of tranexamic acid as an agent for patients with significant bleeding. It is anticipated that the full trial results will be available in 2017. <h3>Disclosure of Interest</h3> None Declared.
Isolated nocturnal desaturation in COPD: prevalence and impact on quality of life and sleep
Authors: C A Lewis, W Fergusson, T Eaton, I Zeng, J Kolbe
Journal: Thorax (2008)

<h3>Background and aims:</h3> The clinical impact of nocturnal desaturation on health related quality of life (HRQL) and sleep in chronic obstructive pulmonary disease (COPD) has been little studied. The aim of this study was to evaluate the prevalence and clinical impact of nocturnal desaturation in a typical outpatient population with COPD. <h3>Patients and methods:</h3> Between 2002 and 2005, consecutive patients with COPD attending outpatient services at the study centre underwent resting oximetry if they were not on domiciliary oxygen therapy. If their resting saturations were less than 95%, overnight pulse oximetry was performed. Significant nocturnal desaturation was defined as spending more than 30% of at least one of two nights with a saturation of less than 90%. The Chronic Respiratory Questionnaire (CRQ) and Short Form 36 (SF36) were used to assess HRQL, and the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep (FOSQ) questionnaires were used to assess sleep quality and daytime function. <h3>Results:</h3> Of 1104 patients, 803 underwent resting oximetry and 79 had resting oxygen saturations of less than 95%. Of these, 59 agreed to undergo overnight oximetry (mean age 70 years, forced expiratory volume in 1 s 37.2% predicted, resting Po<sub>2</sub> on air 8.9 kPa). Significant nocturnal desaturation was seen in 29 (49.2%) of the 59 subjects. Assuming the less hypoxic patients do not have nocturnal desaturation, the prevalence of nocturnal desaturation in the whole clinic population could be estimated at 4.8%. There were no significant differences in CRQ, SF36, PSQI, ESS or FOSQ scores for desaturators compared with non-desaturators. <h3>Conclusion:</h3> Significant nocturnal desaturation was common in patients with COPD with resting saturations of less than 95%, but was estimated to have a prevalence of less than 5% in the whole outpatient population. Nocturnal desaturation was not associated with impairment of HRQL, sleep quality or daytime function.
Adjuvant Trastuzumab in HER2-Positive Breast Cancer
Authors: Dennis Slamon, Wolfgang Eiermann, Nicholas Robert, Tadeusz Pienkowski, Miguel Martin, Michael Press, John Mackey, John Glaspy, Arlene Chan, Marek Pawlicki, Tamas Pinter, Vicente Valero, Mei-Ching Liu, Guido Sauter, Gunter von Minckwitz, Frances Visco, Valerie Bee, Marc Buyse, Belguendouz Bendahmane, Isabelle Tabah-Fisch, Mary-Ann Lindsay, Alessandro Riva, John Crown
Journal: New England Journal of Medicine (2011)

Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).
Mechanisms of bradykinin-induced contraction in human fetal lung fibroblasts
Authors: L. Petecchia, F. Sabatini, C. Usai, S. Carnevali, M. Ognibene, C. Vanni, A. Eva, L.M. Fabbri, G.A. Rossi, F.L.M. Ricciardolo
Journal: European Respiratory Journal (2010)

Bradykinin (BK) induces fibroblast contraction but the structural changes and intracellular mechanisms involved have not been completely explored. We stimulated HFL-1 fibroblasts with BK to assess: 1) fibroblast contractility; 2) the role of α-smooth muscle actin (SMA) in contraction by small interfering RNA (siRNA); 3) α-SMA protein expression; 4) α-SMA and F-actin structure; 5) intracellular calcium concentration ([Ca 2+ ] i ); and 6) phosphorylated myosin light-chain (pMLC) and MLC kinase (MLCK) expression. BK triggered concentration- and time-dependent fibroblast gel contraction in conjunction with α-SMA over expression, but not in α-SMA-siRNA-treated cells. BK also increased α-SMA + and F-actin + cell number and stress fibre polymerisation (detectable at 5–60 min). These BK-induced changes were associated with an increase in [Ca 2+ ] i , which peaked within 15 s, and activation of pMLC, which was detectable at 5–60 min. No MLCK content modification was observed. The different manifestations of the BK-induced fibroblast activation were downregulated at different levels (25–100%) by HOE140, a specific BK B2 receptor (B2R) antagonist and by the Ca 2+ chelator, EGTA. Thus, BK-induced fibroblast contraction, associated with differentiation into α-SMA + myofibroblasts, is mediated through the activation of the B2R and involves the Ca 2+ /calmodulin pMLC-dependent pathway.
Long-Term Remission of HIV-Associated Primary CNS Lymphoma Achieved With Highly Active Antiretroviral Therapy Alone
Authors: Giovanna Travi, Andrés J.M. Ferreri, Paola Cinque, Simonetta Gerevini, Maurilio Ponzoni, Maria Rosa Terreni, Adriano Lazzarin, Fulvio Crippa
Journal: Journal of Clinical Oncology (2012)
Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease
Authors: Rebecca M. Hill, Sanne Kuijper, Janet C. Lindsey, Kevin Petrie, Ed C. Schwalbe, Karen Barker, Jessica K.R. Boult, Daniel Williamson, Zai Ahmad, Albert Hallsworth, Sarra L. Ryan, Evon Poon, Simon P. Robinson, Ruth Ruddle, Florence I. Raynaud, Louise Howell, Colin Kwok, Abhijit Joshi, Sarah Leigh Nicholson, Stephen Crosier, David W. Ellison, Stephen B. Wharton, Keith Robson, Antony Michalski, Darren Hargrave, Thomas S. Jacques, Barry Pizer, Simon Bailey, Fredrik J. Swartling, William A. Weiss, Louis Chesler, Steven C. Clifford
Journal: Cancer Cell (2014)

We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.
Complement C1s activation in degenerating articular cartilage of rheumatoid arthritis patients: immunohistochemical studies with an active form specific antibody
Authors: K. Nakagawa, H. Sakiyama, T. Tsuchida, K. Yamaguchi, T. Toyoguchi, R. Masuda, H. Moriya
Journal: Annals of the Rheumatic Diseases (1999)

This paper reports incidence of cancer in employees of the Australian petroleum industry from 1981 to 1989. Two surveys by personal interview incorporated more than 15,000 employees, representing 92% of the eligible population. Subjects were included in the analysis after completing five years of service in the industry. At the time of this report the cohort did not include sufficiently large numbers of women for useful analysis; results presented are restricted to the men. On 31 December 1989, 50,254 person-years of observation had accumulated in the men with 152 incident cancers reported. The standardised incidence ratio (SIR) analysis showed overall cancer rates close to those of the national population. Whereas deficits were seen in some cancer sites, notably lung cancer (SIR 0.5, 95% confidence internal (95% CI) 0.3-0.9), incidence rates for some other cancer sites suggested increased risk. An excess of observed over expected cases was present in all subcategories of lymphohaematopoietic cancer except Hodgkin9s disease (no cases), and was most apparent in myeloid leukaemia (SIR 4.0, 95% CI 1.6-8.2). The other major site with a raised number of cases observed over expected was melanoma (SIR 1.4, 95% CI 0.8-2.1).
Reovirus 3 and neonatal biliary disease: Discussion of divergent results
Authors: Rachel Morecki, Joy Glaser
Journal: Hepatology (1989)

Infection with reovirus 3 (Reo-3) has been suggested as the cause of extrahepatic biliary atresia and idiopathic neonatal hepatitis but confirmation has been lacking. Therefore we have searched for a specific anti-Reo-3 antibody response in the sera of patients with biliary atresia or neonatal hepatitis and for Reo-3 antigens in their hepatobiliary tissues. Sera from 23 infants with extrahepatic biliary atresia, 12 with neonatal hepatitis, 30 age-matched control patients with other liver diseases, and 55 control patients without liver disease were tested by an enzyme-linked immunosorbent assay for total (IgA, IgG, and IgM) anti-Reo-antibodies; sera of infants younger than 6 months of age were tested also for IgM anti-Reo-3 antibodies alone. There was no difference between either total or IgM anti-Reo-3 antibody levels in infants with extrahepatic biliary atresia or neonatal hepatitis and levels in control infants. Reo-3 antigens were not detected in the hepatobiliary tissues of 19 infants (18 with biliary atresia, one with neonatal hepatitis) by an immunoperoxidase method that readily demonstrated Reo-3 in control in fected HEp-G2 cells. Our data do not support a relationship between neonatal liver diseases and infection with Reo-3.