tbuckley/cabot-search huggingface dataset:
Altered Hapten Ligands Antagonize Trinitrophenyl-specific Cytotoxic T Cells and Block Internalization of Hapten-specific Receptors
Authors: Tobias Preckel, Rudolf Grimm, Stefan Martin, Hans Ulrich Weltzien
Journal: The Journal of Experimental Medicine (1997)

Low molecular chemicals (haptens) frequently cause T cell–mediated adverse immune reactions. Our previous work provided evidence that hapten-specific T cells, in analogy to those specific for nominal peptide antigens, direct their TCR towards hapten-modified, MHC-associated peptides. We now demonstrate that trinitrophenyl (TNP)-specific, class I MHC–restricted CTL from mice may exhibit exquisite specificity for subtle structural details of these hapten determinants, surpassing even the specificity of immunoglobulins. More importantly, these CTL could be antagonized by ligands altered either in their peptide sequence or in their hapten structure. The system was employed to examine the molecular basis of T cell antagonism. Whereas agonists resulted in a dose-dependent downregulation of TCR in different mouse T cell clones, antagonistic peptides totally failed to do so despite engaging the specific TCR. Moreover, simultaneous presentation of antagonist and agonist on the same antigen presenting cell prevented TCR internalization. No signs of anergy or functional receptor inactivation were observed in CTL treated with antagonist-loaded target cells. Based on a serial triggering model of T cell activation, our data favor a model in which antagonists block T cell functions by competitively engaging the specific TCR in unproductive interactions.
Decisions to follow a rule
Authors: Paul Weirich
Journal: Behavioral and Brain Sciences (2002)

Rachlin favors following patterns over making decisions case by case. However, his accounts of self-control and altruism do not establish the rationality of making decisions according to patterns. The best arguments for using patterns as a standard of evaluation appeal to savings in cognitive costs and compensation for irrational dispositions. What the arguments show depends on how they are elaborated and refined.
Adaptive Mechanisms That Preserve Cardiac Function in Mice Without Myoglobin
Authors: Annette P. Meeson, Nina Radford, John M. Shelton, Pradeep P. A. Mammen, J. Michael DiMaio, Kelley Hutcheson, Yanfeng Kong, Joel Elterman, R. Sanders Williams, Daniel J. Garry
Journal: Circulation Research (2001)

Abstract —Mice lacking myoglobin survive to adulthood and meet the circulatory demands of exercise and pregnancy without cardiac decompensation. In the present study, we show that many myoglobin-deficient embryos die in utero at midgestation with signs of cardiac failure. Fetal mice that survive to gestational day 12.5, however, suffer no subsequent excess mortality. Survival in the absence of myoglobin is associated with increased vascularity and the induction of genes encoding the hypoxia-inducible transcription factors 1α and 2, stress proteins such as heat shock protein 27, and vascular endothelial growth factor. These adaptations are evident in late fetal life, persist into adulthood, and are sufficient to maintain normal myocardial oxygen consumption during stressed conditions. These data reveal that myoglobin is necessary to support cardiac function during development, but adaptive responses evoked in some animals can fully compensate for the defect in cellular oxygen transport resulting from the loss of myoglobin.
Coupled Pacing and Coupled Pacing with Concealed Conduction
Authors: LEWIS B. SHEINER, RICHARD J. STOCK
Journal: Circulation (1966)

In the case reported coupled pacing via an intracardiac catheter electrode was undertaken and continued for 28 days in order to slow the rapid ventricular response in atrial fibrillation, refractory to drug management and cardioversion. A new phenomenon was observed in which the coupled stimulus caused cardiac cycle prolongation but elicited neither a mechanical nor a propagated electrical ventricular response. Possible mechanisms of this phenomenon are discussed. Stimulation of the bundle of His or a bundle branch with retrograde, concealed conduction in the A-V node and simultaneous antegrade concealed conduction and block are suggested as the most likely. When this phenomenon was produced after each consecutive spontaneous depolarization, a reduction in ventricular rate resulted without the production of coupled extrasystolic ventricular depolarizations. This constituted a new coupled pacing technique, termed "coupled concealed pacing." The long-term effects of this technique and of conventional coupled pacing and paired stimulation in this patient are also reported.
Prediction and prevention of musculoskeletal injury: a paradigm shift in methodology
Authors: C E Quatman, C C Quatman, T E Hewett
Journal: British Journal of Sports Medicine (2009)

Traditional methods employed to study musculoskeletal injury mechanisms and joint biomechanics utilise in vivo or in vitro techniques. The advent of new technology and improved methods has also given rise to in silico (computer modelling) techniques. Under the current research paradigm, in vivo, in vitro and in silico methods independently provide information regarding the mechanisms and prevention of musculoskeletal injury. However, individually, each of these methods has multiple, inherent limitations and is likely to provide incomplete answers about multifactorial, complex injury conditions. The purpose of this treatise is to review current methods used to study, understand, and prevent musculoskeletal injury and to develop new conceptual-methodological frameworks that may help create a paradigm shift in musculoskeletal injury prevention research. We term the fusion of these three techniques in simulacra amalgama, or simply in sim, meaning a "union of models done on the likeness of phenomena." Anterior cruciate ligament (ACL) injury will be employed as a model example for the utility and applicability of the proposed, synthesised approach. Shifting the current experimental paradigm to incorporate a multifaceted, multidisciplinary, integration of in vivo, in vitro and in silico methods into the proposed in sim approaches may provide a platform for a more comprehensive understanding of the relationships between complex joint biomechanics and observed injury mechanisms.
Survival Benefit of Radical Prostatectomy in Lymph Node–Positive Patients with Prostate Cancer
Authors: Jutta Engel, Patrick J. Bastian, Helmut Baur, Volker Beer, Christian Chaussy, Juergen E. Gschwend, Ralph Oberneder, Karl H. Rothenberger, Christian G. Stief, Dieter Hölzel
Journal: European Urology (2010)
PTEN augments SPARC suppression of proliferation and inhibits SPARC-induced migration by suppressing SHC-RAF-ERK and AKT signaling
Authors: Stacey L. Thomas, Ridwan Alam, Nancy Lemke, Lonni R. Schultz, Jorge A. Gutiérrez, Sandra A. Rempel
Journal: Neuro-Oncology (2010)

SPARC (secreted protein acidic and rich in cysteine) is expressed in all grades of astrocytoma, including glioblastoma (GBM).SPARC suppresses glioma growth but promotes migration and invasion by mediating integrin and growth factor receptor-regulated kinases and their downstream effectors.PTEN (phosphatase and tensin homolog deleted on chromosome 10), which is commonly lost in primary GBMs, negatively regulates proliferation and migration by inhibiting some of the same SPARC-mediated signaling pathways.This study determined whether PTEN reconstitution in PTEN-mutant, SPARC-expressing U87MG cells could further suppress proliferation and tumor growth but inhibit migration and invasion in SPARC-expressing cells in vitro and in vivo, and thereby prolong survival in animals with xenograft tumors.In vitro, PTEN reduced proliferation and migration in both SPARCexpressing and control cells, with a greater suppression in SPARC-expressing cells.PTEN reconstitution suppressed AKT activation in SPARC-expressing and control cells but suppressed the SHC-RAF-ERK signaling pathway only in SPARC-expressing cells.Importantly, coexpression of SPARC and PTEN resulted in the smallest, least proliferative tumors with reduced invasive capacity and longer animal survival.Furthermore, direct inhibition of the AKT and SHC-RAF-ERK signaling pathways suppressed the proliferation and migration of SPARC-expressing cells in vitro.These findings demonstrate that PTEN reconstitution or inhibition of signaling pathways that are activated by the loss of PTEN provide potential therapeutic strategies to inhibit SPARC-induced invasion while enhancing the negative effect of SPARC on tumor growth.
Tissue-Specific Consequences of Cyclin D1 Overexpression in Prostate Cancer Progression
Authors: Yue He, Omar E. Franco, Ming Jiang, Karin Williams, Harold D. Love, Ilsa M. Coleman, Peter S. Nelson, Simon W. Hayward
Journal: Cancer Research (2007)

Abstract The cyclin D1 oncogene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the Rb protein and promotes progression through G1 to S phase of the cell cycle. Several prostate cancer cell lines and a subset of primary prostate cancer samples have increased cyclin D1 protein expression. However, the relationship between cyclin D1 expression and prostate tumor progression has yet to be clearly characterized. This study examined the effects of manipulating cyclin D1 expression in either human prostatic epithelial or stromal cells using a tissue recombination model. The data showed that overexpression of cyclin D1 in the initiated BPH-1 cell line increased cell proliferation rate but did not elicit tumorigenicity in vivo. However, overexpression of cyclin D1 in normal prostate fibroblasts (NPF) that were subsequently recombined with BPH-1 did induce malignant transformation of the epithelial cells. The present study also showed that recombination of BPH-1 + cyclin D1–overexpressing fibroblasts (NPFcyclin D1) resulted in permanent malignant transformation of epithelial cells (BPH-1NPF-cyclin D1 cells) similar to that seen with carcinoma-associated fibroblasts (CAF). Microarray analysis showed that the expression profiles between CAFs and NPFcyclin D1 cells were highly concordant including cyclin D1 up-regulation. These data indicated that the tumor-promoting activity of cyclin D1 may be tissue specific. [Cancer Res 2007;67(17):8188–97]
A pitfall in purulent arthritis brought out in Kingella kingae infection of the knee.
Authors: I Salminen, R von Essen, K Koota, A Nissinen
Journal: Annals of the Rheumatic Diseases (1984)

A description of the protracted course of kingella monoarthritis is given as an illustration of the importance of accounting for the slow growth, low viable numbers, and fastidious culture requirements of microbes that may be encountered in synovial samples. The practice of carrying out synovial fluid cultures in the same way as blood cultures is recommended.
A Two-stage Personal Cyclone Sampler for the Collection of Fungal Aerosols and Direct ELISA and PCR Sample Analysis
Authors: D. Schmechel, W.G. Lindsley, T.B. Chen, F.M. Blachere, B.J. Green, R.A. Brundage, D.H. Beezhold
Journal: Journal of Allergy and Clinical Immunology (2007)
Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
Authors: Daniel F Gudbjartsson, Unnur S Bjornsdottir, Eva Halapi, Anna Helgadottir, Patrick Sulem, Gudrun M Jonsdottir, Gudmar Thorleifsson, Hafdis Helgadottir, Valgerdur Steinthorsdottir, Hreinn Stefansson, Carolyn Williams, Jennie Hui, John Beilby, Nicole M Warrington, Alan James, Lyle J Palmer, Gerard H Koppelman, Andrea Heinzmann, Marcus Krueger, H Marike Boezen, Amanda Wheatley, Janine Altmuller, Hyoung Doo Shin, Soo-Taek Uh, Hyun Sub Cheong, Brynja Jonsdottir, David Gislason, Choon-Sik Park, Linda M Rasmussen, Celeste Porsbjerg, Jakob W Hansen, Vibeke Backer, Thomas Werge, Christer Janson, Ulla-Britt Jönsson, Maggie C Y Ng, Juliana Chan, Wing Yee So, Ronald Ma, Svati H Shah, Christopher B Granger, Arshed A Quyyumi, Allan I Levey, Viola Vaccarino, Muredach P Reilly, Daniel J Rader, Michael J A Williams, Andre M van Rij, Gregory T Jones, Elisabetta Trabetti, Giovanni Malerba, Pier Franco Pignatti, Attilio Boner, Lydia Pescollderungg, Domenico Girelli, Oliviero Olivieri, Nicola Martinelli, Bjorn R Ludviksson, Dora Ludviksdottir, Gudmundur I Eyjolfsson, David Arnar, Gudmundur Thorgeirsson, Klaus Deichmann, Philip J Thompson, Matthias Wjst, Ian P Hall, Dirkje S Postma, Thorarinn Gislason, Jeffrey Gulcher, Augustine Kong, Ingileif Jonsdottir, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2009)
Interventions to Improve Medication Adherence in Schizophrenia
Authors: Annette Zygmunt, Mark Olfson, Carol A Boyer, David Mechanic
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Although nonadherence with the antipsychotic medication regimen is a common barrier to the effective treatment for schizophrenia, knowledge is limited about how to improve medication adherence. This systematic literature review examined psychosocial interventions for improving medication adherence, focusing on promising initiatives, reasonable standards for conducting research in this area, and implications for clinical practice. METHOD: Studies were identified by computerized searches of MEDLINE and PsychLIT for the years between 1980 and 2000 and by manual searches of relevant bibliographies and conference proceedings. Key articles were summarized. RESULTS: Thirteen (33%) of 39 identified studies reported significant intervention effects. Although interventions and family therapy programs relying on psychoeducation were common in clinical practice, they were typically ineffective. Concrete problem solving or motivational techniques were common features of successful programs. Interventions targeted specifically to problems of nonadherence were more likely to be effective (55%) than were more broadly based treatment interventions (26%). One-half (four of eight) of the successful interventions not specifically focused on nonadherence involved an array of supportive and rehabilitative community-based services. CONCLUSIONS: Psychoeducational interventions without accompanying behavioral components and supportive services are not likely to be effective in improving medication adherence in schizophrenia. Models of community care such as assertive community treatment and interventions based on principles of motivational interviewing are promising. Providing patients with concrete instructions and problem-solving strategies, such as reminders, self-monitoring tools, cues, and reinforcements, is useful. Problems in adherence are recurring, and booster sessions are needed to reinforce and consolidate gains.
SEARCH: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Sorafenib Plus Erlotinib in Patients With Advanced Hepatocellular Carcinoma
Authors: Andrew X. Zhu, Olivier Rosmorduc, T.R. Jeffry Evans, Paul J. Ross, Armando Santoro, Flair Jose Carrilho, Jordi Bruix, Shukui Qin, Paul J. Thuluvath, Josep M. Llovet, Marie-Aude Leberre, Markus Jensen, Gerold Meinhardt, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2014)

To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma (HCC) in a multicenter, multinational, randomized, phase III trial.
Evaluation of Excess Statistical Significance in Meta-analyses of 98 Biomarker Associations with Cancer Risk
Authors: Konstantinos K. Tsilidis, Stefania I. Papatheodorou, Evangelos Evangelou, John P. A. Ioannidis
Journal: JNCI Journal of the National Cancer Institute (2012)

Numerous biomarkers have been associated with cancer risk. We assessed whether there is evidence for excess statistical significance in results of cancer biomarker studies, suggesting biases.We systematically searched PubMed for meta-analyses of nongenetic biomarkers and cancer risk. The number of observed studies with statistically significant results was compared with the expected number, based on the statistical power of each study under different assumptions for the plausible effect size. We also evaluated small-study effects using asymmetry tests. All statistical tests were two-sided.We included 98 meta-analyses with 847 studies. Forty-three meta-analyses (44%) found nominally statistically significant summary effects (random effects). The proportion of meta-analyses with statistically significant effects was highest for infectious agents (86%), inflammatory (67%), and insulin-like growth factor (IGF)/insulin system (52%) biomarkers. Overall, 269 (32%) individual studies observed nominally statistically significant results. A statistically significant excess of the observed over the expected number of studies with statistically significant results was seen in 20 meta-analyses. An excess of observed vs expected was observed in studies of IGF/insulin (P ≤ .04) and inflammation systems (P ≤ .02). Only 12 meta-analyses (12%) had a statistically significant summary effect size, more than 1000 case patients, and no hints of small-study effects or excess statistical significance; only four of them had large effect sizes, three of which pertained to infectious agents (Helicobacter pylori, hepatitis and human papilloma viruses).Most well-documented biomarkers of cancer risk without evidence of bias pertain to infectious agents. Conversely, an excess of statistically significant findings was observed in studies of IGF/insulin and inflammation systems, suggesting reporting biases.
Dimerization: An Emerging Concept for G Protein–Coupled Receptor Ontogeny and Function
Authors: Stephane Angers, Ali Salahpour, Michel Bouvier
Journal: The Annual Review of Pharmacology and Toxicology (2002)

In the last four to five years, the view that G protein–coupled receptors (GPCRs) function as monomeric proteins has been challenged by numerous studies, which suggests that GPCRs exist as dimers or even higher-structure oligomers. Recently, biophysical methods based on luminescence and fluorescence energy transfer have confirmed the existence of such oligomeric complexes in living cells. Although no consensus exists on the role of receptor dimerization, converging evidence suggests potential roles in various aspects of receptor biogenesis and function. In several cases, receptors appear to fold as constitutive dimers early after biosynthesis, whereas ligand-promoted dimerization at the cell surface has been proposed for others. The reports of heterodimerization between receptor subtypes suggest a potential level of receptor complexity that could account for previously unexpected pharmacological diversities. In addition to fundamentally changing our views on the structure and activation processes of GPCRs, the concept of homo- and heterodimerization could have dramatic impacts on drug development and screening.
Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists
Authors: A Lucía, J Hoyos, A Santalla, M Pérez, A Carvajal, J L Chicharro
Journal: British Journal of Sports Medicine (2002)

Objective: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists. Methods: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W/12 s, averaging 25 W/min). Heart rate (HR), gas exchange parameters, and blood variables (lactate, pH, P 50 of the oxyhaemoglobin dissociation curve, and K + ) were measured during the tests. Results: A HRDP was shown in 56% of subjects at about 88% of their maximal HR (HRDP group; n = 9) but was linear in the rest (No-HRDP group; n = 7). In the HRDP group, the slope of the HR-workload regression line above the HRDP correlated inversely with levels of K + at the maximal power output ( r = −0.67; p&lt;0.05). Conclusions: The HRDP phenomenon is associated, at least partly, with exercise induced hyperkalaemia.
Chronic widespread pain in the population: a seven year follow up study
Authors: A C Papageorgiou
Journal: Annals of the Rheumatic Diseases (2002)

To document the natural course of chronic widespread pain (CWP) in a general population sample over a seven year period and to identify comorbidities which predict persistence.A mailed survey questionnaire returned by 2334 adults registered with two general practices was used to obtain information on pain status (no pain, regional pain, or CWP) and other health and pain symptoms. Seven years later a second questionnaire was sent to responders who were still registered with the same general practice, asking about their current pain status.Information was obtained for 1386 adults (an adjusted response of 93%). The prevalence of CWP was similar for both surveys at 11% and 10% respectively. Of those with CWP initially, a third recorded CWP on the second survey and 15% were pain free. Only 2% of subjects with no initial pain had developed CWP at follow up. Of subjects with CWP on the initial survey who were aged over 50 years and reported dry eyes or mouth and daytime tiredness, 77% reported CWP seven years later. This contrasts with a persistence of only 9% for those aged under 50 and with neither symptom recorded at initial survey.The proportion of subjects from a general population sample changing from CWP to no pain, or vice versa, over a seven year period was very low. This suggests that pain, once established, is likely to persist (or recur) especially if accompanied by other somatic symptoms and older age.
High risk and rapid appearance of multidrug resistance during tuberculosis treatment in Moldova
Authors: Helen E. Jenkins, Valeriu Crudu, Viorel Soltan, Ana Ciobanu, Liliana Domente, Ted Cohen
Journal: European Respiratory Journal (2014)

Multidrug-resistant tuberculosis (MDR-TB) is a serious problem in the former Soviet Union and may appear during TB treatment. We aimed to estimate the prevalence of, timing of and factors associated with MDR-TB diagnosis during TB treatment in Moldova, which was part of the former Soviet Union. We analysed data on 3 754 confirmed non-MDR-TB cases (between January 1, 2007 and December 31, 2010) in the Moldovan TB surveillance database, where patients provided sputum specimens for drug-susceptibility testing, multiple times, during treatment. We estimated the percentage of individuals with confirmed baseline non-MDR-TB that were diagnosed with MDR-TB during treatment, documented the time at which MDR-TB was diagnosed, and used a failure-time model to identify factors associated with MDR-TB diagnosis. Between 7.2% and 9.2% of initially non-MDR-TB cases were diagnosed with MDR-TB during treatment. Half of these MDR-TB diagnoses occurred with 3 months of the initial diagnosis. An increased MDR-TB risk during treatment was associated with baseline resistance to first-line TB drugs (linear increase in risk per additional drug), previous incarceration and HIV co-infection. MDR can appear rapidly during TB treatment. Policy considerations should emphasise management during early treatment by increasing ambulatory TB treatment to prevent nosocomial transmission, and ensuring universal rapid diagnostics access to prevent acquisition and transmission of drug resistance.
Beyond the Learning Curve of the Retzius-sparing Approach for Robot-assisted Laparoscopic Radical Prostatectomy: Oncologic and Functional Results of the First 200 Patients with ≥1 Year of Follow-up
Authors: Antonio Galfano, Dario Di Trapani, Francesco Sozzi, Elena Strada, Giovanni Petralia, Manuela Bramerio, Assunta Ascione, Marcello Gambacorta, Aldo Massimo Bocciardi
Journal: European Urology (2013)