tbuckley/cabot-search huggingface dataset:
Validation of the ABILHAND questionnaire as a measure of manual ability in patients with rheumatoid arthritis
Authors: P. Durez, V. Fraselle, F. Houssiau, J.-L. Thonnard, H. Nielens, M. Penta
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> Hand and upper limb involvement is common in patients with rheumatoid arthritis (RA). However, its impact on manual activities of daily life has not been fully evaluated. A measure of manual ability was developed, through the Rasch measurement model, by adapting and validating the ABILHAND questionnaire, which measures the patient's perceived difficulty in performing everyday manual activities. <b>Methods:</b> 112 patients with RA were evaluated. The following tests were performed: the ABILHAND questionnaire, the Health Assessment Questionnaire (HAQ), the Jamar grip and key pinch strength tests, the Box and Block dexterity test and the Purdue pegboard dexterity test. In total, 35 patients were reassessed to determine the test–retest reliability of the ABILHAND, and 6 patients were studied before and after therapy with tumour necrosis factor (TNF) blockers to address sensitivity to change. <b>Results:</b> The Rasch refinement of the ABILHAND led to a selection of 27 items rated on a 3-point scale. The resulting ability scale was targeted to the ability of the patients. The item-difficulty hierarchy was stable across demographic and clinical subgroups and over time. Grip and key pinch strength and manual and digital dexterity on both hands were significantly, though moderately, correlated with the ABILHAND measures. Manual ability was also significantly related to the number of affected hands, disease duration, tender and swollen joint counts on upper limbs, disease activity and the HAQ. Sensitivity to change was demonstrated in patients treated with TNF blockers, commensurate with their clinical improvement. <b>Conclusion:</b> The ABILHAND questionnaire is a clinically valid person-centred measure of manual ability that could be useful in longitudinal RA studies.
Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex
Authors: Rita Z. Goldstein, Nora D. Volkow
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. CONCLUSIONS: These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward.
Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor
Authors: Gang Lu, Qing Zhang, Ying Huang, Jiaxi Song, Ross Tomaino, Tobias Ehrenberger, Elgene Lim, Wenbin Liu, Roderick T. Bronson, Michaela Bowden, Jane Brock, Ian E. Krop, Deborah A. Dillon, Steven P. Gygi, Gordon B. Mills, Andrea L. Richardson, Sabina Signoretti, Michael B. Yaffe, William G. Kaelin
Journal: Cancer Cell (2014)
Distinct Effects of Methotrexate and Etanercept on the B Cell Compartment in Patients With Juvenile Idiopathic Arthritis
Authors: Stephanie Glaesener, Tâm D. Quách, Nils Onken, Frank Weller‐Heinemann, Frank Dressler, Hans‐Iko Huppertz, Angelika Thon, Almut Meyer‐Bahlburg
Journal: Arthritis & Rheumatology (2014)

B cells have been shown to play an important role in the pathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). Current treatments include the disease-modifying antirheumatic drugs methotrexate (MTX) and tumor necrosis factor α inhibition with etanercept. This study was undertaken to determine how these drugs influence the B cell compartment in patients with JIA. B cell subpopulations and follicular helper T (Tfh) cells in the peripheral blood of JIA patients were investigated by multicolor flow cytometry. Serum immunoglobulin and BAFF levels were determined by enzyme-linked immunosorbent assay. There was a significant decrease in transitional B cells and significantly lower serum immunoglobulin levels in patients receiving MTX than in untreated patients and those receiving etanercept. In contrast, etanercept treatment had no effect on most of the B cell subpopulations, but resulted in significantly lower BAFF levels and increased numbers of Tfh cells. Thus, our findings indicate an unexpected and previously unknown direct effect of low-dose MTX on B cells, whereas etanercept had a more indirect influence. Our results contribute to a better understanding of the potency of MTX in autoantibody-mediated autoimmune disease and present a possible mechanism of prevention of the development of drug-induced antibodies to biologic agents. The finding that MTX and etanercept affect the B cell compartment differently supports the notion that combination therapy with etanercept and MTX is more effective than monotherapy.
Cooperative Disengagement of Fas and Intercellular Adhesion Molecule-1 Function in Neoplastic Cells Confers Enhanced Colonization Efficiency
Authors: Kebin Liu, Sheila A. Caldwell, Scott I. Abrams
Journal: Cancer Research (2005)

Understanding the mechanisms of tumor progression is crucial toward the development of therapeutic interventions. Although the loss of sensitivity to cell death is a hallmark of neoplastic progression, it is likely one of several essential features that underlie a malignantly proficient or aggressive tumorigenic phenotype. Here, we identified intercellular adhesion molecule-1 (ICAM-1) as a molecule with expression coordinately regulated with Fas and inversely correlated with malignant phenotype between matched pairs of differentially aggressive malignant subpopulations in three mouse models. To determine whether coordinate expression of Fas and ICAM-1 regulated malignant behavior, tumor sublines were produced that expressed either lower levels of both Fas and ICAM-1, lower levels of Fas, or lower levels of ICAM-1 and then assessed for metastatic lung tumor growth. Tumor sublines rendered both Fas incompetent and ICAM-1 incompetent displayed significantly higher numbers of tumor nodules compared with tumor sublines separately expressing low levels of Fas or ICAM-1. However, all tumor sublines regardless of their Fas and ICAM-1 levels comparably infiltrated the lung, suggesting that Fas- and ICAM-1-based interactions ultimately influenced lung colonization efficiency. Overall, these data suggested that both Fas and ICAM-1 pathways cooperated to regulate tumor progression and that the coordinate down-regulation of Fas and ICAM-1 intensified malignant progression at the level of colonization. Thus, a Fas(lo)ICAM-1(lo) phenotype may be characteristic of at least certain advancing, immune-resistant neoplastic subpopulations.
Mitochondrial uncoupling protein 2 mediates temperature heterogeneity in atherosclerotic plaques
Authors: T. J.L. Van De Parre, W. Martinet, S. Verheye, M. M. Kockx, G. Van Langenhove, A. G. Herman, G. R.Y. De Meyer
Journal: Cardiovascular Research (2007)

Rupture-prone atherosclerotic plaques show an elevated temperature, but a molecular explanation for this phenomenon is unknown. Here, we investigated whether mitochondrial uncoupling protein 2 (UCP2) could be involved because this protein is a macrophage homologue of thermogenin in brown fat tissue.Immunohistochemistry, western blotting, and real-time quantitative polymerase chain reaction were used to detect UCP2 expression in human and rabbit atherosclerotic plaques. Temperature was measured in plaques with thermography catheters and in cultured cells with precision thermometers. UCP2 was abundantly expressed in subendothelial macrophages of atherosclerotic plaques but not in deeper layers of the plaque. Ex vivo temperature measurements in atherosclerotic rabbit thoracic aorta demonstrated a correlation between local plaque temperature, total macrophage mass, and UCP2 expression. In vitro, chemical uncoupling of macrophages with sodium cyanide resulted in heat production (DeltaT = 0.13 +/- 0.04 degrees C vs. controls). Also, overexpression of UCP2 in cultured cells led to a similar increase in temperature.Our findings provide evidence that temperature heterogeneity in atherosclerotic plaques is at least in part attributed to UCP2 expression in macrophages. The heat generated might be used to detect unstable, macrophage-rich, atherosclerotic plaques via thermography.
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
Authors: Peter J. Turnbaugh, Vanessa K. Ridaura, Jeremiah J. Faith, Federico E. Rey, Rob Knight, Jeffrey I. Gordon
Journal: Science Translational Medicine (2009)

A translational medicine pipeline is described where human gut microbial communities and diets are re-created in gnotobiotic mice and the impact on microbe and host is defined using metagenomics.
Hydrophilic Camptothecin Analogs That Form Extremely Stable Cleavable Complexes with DNA and Topoisomerase I
Authors: Randy M. Wadkins, David Bearss, Govindarajan Manikumar, Mansukhlal C. Wani, Monroe E. Wall, Daniel D. Von Hoff
Journal: Cancer Research (2004)

Abstract Camptothecin (CPT) analogs that form more stable ternary complexes with DNA and topoisomerase I (termed cleavable complexes) show greater activity in their ability to inhibit tumor cell line growth in preclinical studies. Based on our earlier work, we hypothesized that analogs bearing hydrogen bonding moieties at the 7- through 10-position of CPT would result in more stable cleavable complexes. Consequently, we synthesized analogs with 7-mono-, 7-di-, and 7-trihydroxymethylaminomethyl groups. These analogs showed increasing cleavable complex stability as the number of hydroxyl groups was increased. The 7-trihydroxymethylaminomethyl analog of 10,11-methylenedioxycamptothecin (THMAM-MD) showed remarkable ternary complex stability with a half-life of 116 minutes. This is an order of magnitude more stable than any previously examined analog. Our in vitro analysis demonstrated that these analogs were all potent topoisomerase I poisons and could inhibit tumor cell growth in culture. We studied the effects of THMAM-MD in vivo in severe combined immunodeficient mice bearing HT-29 colon cancer and MiaPaCa-2 pancreatic cancer tumors. The THMAM-MD analog showed excellent, persisting activity in inhibiting tumor growth with both lines. Taken together, our results suggest that CPTs with hydrophilic, hydrogen-bonding groups at the 7-position hold the promise of excellent clinical activity.
Existential Psychotherapy for Patients With Advanced Cancer: Facing the Future and the Past
Authors: David Spiegel
Journal: Journal of Clinical Oncology (2015)

Breitbart et al 1 are to be congratulated for their important contribution to the literature on existentially focused psychotherapy for patients with advanced cancer.They have provided further compelling evidence that discussion of death and meaning in life decreased rather than increased depression and improved quality of life at 2-month follow-up, as their intent-to-treat analysis indicated.Anxiety was not affected, and less conservative analyses involving only those who attended three or more sessions indicated significant treatment effects on spiritual well-being, hopelessness, desire for hastened death, and physical symptom distress as well.The study is also notable for having supportive group psychotherapy as the control condition.However, clarification is needed regarding the foundation of research to which the study adds.The authors wrote, "Several psychotherapeutic interventions have focused on patients with advanced or terminal illness, but these studies have often generated modest results (eg, small treatment effects, inconsistent findings across outcome variables) and have typically relied on small samples (eg, Ͻ 100 participants)." 1(p749) The first article they cite, a study from our laboratory, was a randomized clinical trial involving 125 women with metastatic breast cancer. 2It was a replication of our earlier finding of improvement in mood involving 86 similar women with advanced breast cancer. 3The results were medium-sized effects, in a large sample, based on intent-to-treat analysis, and were consistent with our prior work, notably in the reduction in anxiety.Breitbart et al then commented, "A number of interventions focused primarily on existential issues have not targeted patients with advanced or terminal cancer." 1(5][6] (Despite the incidental similarity in name, this existential group therapy approach is quite different from the supportive group psychotherapy used as the control condition in the Breitbart et al study.)Two other major clinical trials involving the use of SEGT in large samples of women with metastatic breast cancer have been conducted but were not cited.Kissane et al 7 randomly assigned 485 women with advanced breast cancer to SEGT plus three classes of relaxation therapy or relaxation therapy alone.SEGT prevented new DSM-IV depressive disorders (P ϭ .002),reduced hopeless-helplessness (P ϭ .004),decreased trauma symptoms (P ϭ .04),and improved social functioning (P ϭ .03).Goodwin et al 8 conducted a seven-site randomized trial of SEGT among 235 women with metastatic breast cancer.The group treatment resulted in a sig-nificant reduction in Total Mood Disturbance on the Profile of Mood States, and produced improvements on the Depression, Tension/ Anxiety, Anger, and Confusion subscales.In addition, Chochinov developed Dignity Therapy to help with psychosocial and existential distress among terminally ill patients.His randomized trial of Dignity
REGULAR CEREBRAL BLOOD FLOW MAPPING WITH 99mTc-LABELLED COMPOUND
Authors: P.J. Ell, I. Cullum, D.C. Costa, P.H. Jarritt, J.M.L. Hocknell, D. Lui, R.F. Jewkes, T.J. Steiner, D.P. Nowotnik, R.D. Pickett, R.D. Neirinckx
Journal: The Lancet (1985)
Gastric marginal zone lymphoma is associated with polymorphisms in genes involved in inflammatory response and antioxidative capacity
Authors: Sara Rollinson, Adam P. Levene, Fiona K. Mensah, Philippa L. Roddam, James M. Allan, Tim C. Diss, Eve Roman, Andrew Jack, Kenneth MacLennan, Michael F. Dixon, Gareth J. Morgan
Journal: Blood (2003)
Mean platelet volume is increased in hyperthyroidism
Authors: H. C. Ford, R. J. Toomath, J. M. Carter, J. W. Delahunt, J. N. Fagerstrom
Journal: American Journal of Hematology (1988)

Abstract In 28 unselected patients with hyperthyroidlsm, platelet count, platelet hematocrft, mean platelet volume, and platelet distribution width were measured at the time of presentation and again when the patients were euthyroid. On return to the euthyroid state, there were highly significant falls in the mean values of the mean platelet volume (16% decline, P &lt; 0.001) and the platelet hematocrit (16% decline, P &lt; 0.001) and a slight but highly significant increase in the mean value of the platelet distribution width (2% increase, P &lt; 0.01). A decline in mean platelet volume was observed in 24 of 28 patients (86%); three patients showed no change. There was no significant change in the mean value of the platelet count. The observed effects of thyrotoxicosis on platets appeared to be largely independent of the well‐known effects on erythrocytes and white blood cells. An increase in mean platelet volume is a regular feature of hyperthyroidism that has not previously been described.
Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRα gene in the X chromosome pseudoautosomal region 1
Authors: Margarita Martinez-Moczygemba, Minh L. Doan, Okan Elidemir, Leland L. Fan, Sau Wai Cheung, Jonathan T. Lei, James P. Moore, Ghamartaj Tavana, Lora R. Lewis, Yiming Zhu, Donna M. Muzny, Richard A. Gibbs, David P. Huston
Journal: The Journal of Experimental Medicine (2008)

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common β chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR α chain, encoded in the X-chromosome pseudoautosomal region 1.
Don't let misinformation derail the trachoma elimination programme
Authors: Solomon Aw, Mabey Dc, Gilbert C, Griffiths U, Mills A, Foster A, West Sk, Courtright P, Feczko J, Alemayehu W, Cross C, Lietman Tm, Haddad D, Harper C, Emerson P, Le Mesurier R, Engels D, Mariotti Sp
Journal: BMJ (2012)

Chisholm and colleagues’ paper is important to policy makers,1 so serious errors in the trachoma analysis require correction.2

Firstly, “mass treatment with azithromycin” for trachoma was defined as azithromycin treatment for all children aged 1-10 years,3 whereas the World Health Organization recommends treatment of all residents.

Secondly, data from a 1998-9 western Nepal trial were extrapolated to estimate effectiveness of mass treatment throughout sub-Saharan Africa and South East Asia.

Thirdly, the …
Challenging Problems in Advanced Malignancy
Authors: B.T. Hennessy, A. Horgan, M. Hogan, J. Barry, S. O Reilly, O. Breathnach
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.10.055 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12915611 Challenging Problems in Advanced Malignancy CASE 4. USE OF POSITRON EMISSION TOMOGRAPHY TO SOLVE A DIAGNOSTIC DILEMMA IN A PATIENT WITH NON-HODGKIN’S LYMPHOMA B.T. HennessyxB.T. HennessySearch for articles by this author , A. HorganxA. HorganSearch for articles by this author , M. HoganxM. HoganSearch for articles by this author , J. BarryxJ. BarrySearch for articles by this author , S. O ReillyxS. O ReillySearch for articles by this author , O. BreathnachxO. BreathnachSearch for articles by this author Show More Cork University Hospital, Wilton, Cork, Ireland https://doi.org/10.1200/JCO.2003.10.055 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Patients Exposed to Rofecoxib and Celecoxib Have Different Odds of Nonfatal Myocardial Infarction
Authors: Stephen E. Kimmel, Jesse A. Berlin, Muredach Reilly, Jane Jaskowiak, Lori Kishel, Jesse Chittams, Brian L. Strom
Journal: Annals of Internal Medicine (2005)

Background: Studies have postulated that cyclooxygenase-2 (COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk (for example, inhibition of prostacyclin production), and some could decrease risk (for example, inhibition of inflammation). Objective: To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction (MI). Design: Case–control study. Setting: 36 hospitals in a 5-county area. Participants: 1718 case-patients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties. Measurements: Self-reported medication use assessed through telephone interviews. Results: The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), was 0.43 (95% CI, 0.23 to 0.79) compared with 1.16 (CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib (adjusted odds ratio for rofecoxib vs. celecoxib, 2.72 [CI, 1.24 to 5.95]; P = 0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen (odds ratio, 3.39 [CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac (odds ratio, 0.77 [CI, 0.40 to 1.48]). Limitations: The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50% of eligible participants completed telephone interviews. Conclusion: Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.
Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL.
Authors: M A Alexander-Miller, G R Leggatt, A Sarin, J A Berzofsky
Journal: The Journal of Experimental Medicine (1996)

Experimental data suggest that negative selection of thymocytes can occur as a result of supraoptimal antigenic stimulation. It is unknown, however, whether such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show that CD8+ effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative inhibition by high dose peptide antigen, leading to apoptotic death mediated by TNF-alpha release. Such inhibition is not reflected in the cytolytic potential of the CTL, since concentrations of antigen that are inhibitory for proliferation promote efficient lysis of target cells. Thus, although CTL have committed to the apoptotic pathway, the kinetics of this process are such that CTL function can occur before death of the CTL. The concentration of antigen required for inhibition is a function of the CTL avidity, in that concentrations of antigen capable of completely inhibiting high avidity CTL maximally stimulate low avidity CTL. Importantly, the inhibition can be detected in both activated and resting CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly to the inhibitory signal as the addition of anti-CD8 antibody restores the proliferative response. Thus, our data support the model that mature CD8+ CTL can accommodate an activation signal of restricted intensity, which, if surpassed, results in deletion of that cell.