tbuckley/cabot-search huggingface dataset:
Anti-tumour necrosis factor antibody treatment does not change serum levels of cortisol binding globulin in patients with rheumatoid arthritis but it increases androstenedione relative to cortisol
Authors: R H Straub
Journal: Annals of the Rheumatic Diseases (2005)

Cortisol binding globulin (CBG) is produced by liver cells and is inhibited by proinflammatory cytokines such as interleukin (IL) 6. CBG serum levels are typically low during prolonged inflammatory processes. Thus, observed changes of cortisol during anti-tumour necrosis factor (TNF) treatment may be related to changes of CBG in rheumatoid arthritis (RA).To investigate the course of CBG during anti-TNF treatment in RA.13 patients with longstanding RA, without prior prednisolone treatment, were included in this longitudinal study with subcutaneous adalimumab.Treatment with anti-TNF markedly decreased clinical markers of inflammation and serum IL6. Serum levels of cortisol, CBG, and the ratio of cortisol/CBG did not change markedly, whereas the ratio of serum CBG/IL6 increased (p = 0.004). In parallel, levels of adrenocorticotropic hormone decreased during the observation period. The ratio serum androstenedione/serum cortisol increased during the study (p = 0.036).During anti-TNF treatment relatively normal levels of CBG and a normal ratio of CBG/cortisol are found. Changes of cortisol in relation to IL6 during anti-TNF treatment, seen previously, may not be related to changes of CBG.
Reading <i>Semantic Cognition</i> as a theory of concepts
Authors: Jesse Snedeker
Journal: Behavioral and Brain Sciences (2008)

Abstract Any theory of semantic cognition is also a theory of concepts. There are two ways to construe the models presented by Rogers &amp; McClelland (R&amp;M) in Semantic Cognition . If we construe the input and output representations as concepts, then the models capture knowledge acquisition within a stable set of concepts. If we construe the hidden-layer representations as concepts, the models provide a simulation of conceptual change.
Variable phenotypic presentation of iron overload in H63D homozygotes: are genetic modifiers the cause?
Authors: P Aguilar-Martinez, M Bismuth, M C Picot, C Thelcide, G-P Pageaux, F Blanc, P Blanc, J-F Schved, D Larrey
Journal: Gut (2001)

First considered as a polymorphism of the HFE gene, the H63D mutation is now widely recognised as a haemochromatosis associated allele. But few H63D homozygotes with clinical manifestations of hereditary haemochromatosis (HH) have been reported. Concurrently, an increasing number of genes have been shown to interact with HFE in iron metabolism.To describe the clinical expression of iron overload (IO) associated with H63D homozygosity, and search for potential genetic modifiers (within the HFE or other genes) that could explain the variability of the phenotypes.We retrospectively analysed the clinical phenotype of 56 H63D homozygotes referred for a personal or family history of IO. For each subject we examined intragenic HFE haplotypes and transferrin receptor (TfR) gene polymorphisms and searched for the Y250X mutation on the TFR2 gene. Additionally, we sequenced the HFE gene of H63D homozygotes with HH.Fifty of 56 subjects had biological and/or clinical abnormalities of iron metabolism. Up to two thirds of patients (n=34) had no acquired cause of IO. Among these, 12 had a phenotypic diagnosis of HH. In the iron loaded group there was a strong prevalence of male patients. No correlation was found between the potential genetic modifiers and phenotypes. No additional mutation of HFE was identified.The variable phenotypes associated with H63D homozygosity do not appear to be linked to other HFE mutations, to the TFR2 Y250X mutation, or to HFE or TfR gene intragenic polymorphisms. The exact role of H63D homozygosity in IO and HH needs to be further investigated in unselected populations.
New evidence of risk factors for community-acquired pneumonia: a population-based study
Authors: J. Almirall, I. Bolíbar, M. Serra-Prat, J. Roig, I. Hospital, E. Carandell, M. Agustí, P. Ayuso, A. Estela, A. Torres
Journal: European Respiratory Journal (2008)

The aim of the present study was to identify risk factors for community-acquired pneumonia (CAP), with special emphasis on modifiable risk factors and those applicable to the general population. A population-based, case–control study was conducted, with a target population of 859,033 inhabitants aged &gt;14 yrs. A total of 1,336 patients with confirmed CAP were matched to control subjects by age, sex and primary centre over 1 yr. In the univariate analysis, outstanding risk factors were passive smoking in never-smokers aged &gt;65 yrs, heavy alcohol intake, contact with pets, households with &gt;10 people, contact with children, interventions on the upper airways and poor dental health. Risky treatments included amiodarone, N -acetylcysteine and oral steroids. Influenza and pneumococcal vaccine, and visiting the dentist were protective factors. Multivariable analysis confirmed cigarette smoking, usual contact with children, sudden changes of temperature at work, inhalation therapy (particularly containing steroids and using plastic pear-spacers), oxygen therapy, asthma and chronic bronchitis as independent risk factors. Interventions for reducing community-acquired pneumonia should integrate health habits and lifestyle factors related to household, work and community, together with individual clinical conditions, comorbidities and oral or inhaled regular treatments. Prevention would include vaccination, dental hygiene and avoidance of upper respiratory colonisation.
Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer
Authors: Julia H. Hayes, Daniel A. Ollendorf, Steven D. Pearson, Michael J. Barry, Philip W. Kantoff, Pablo A. Lee, Pamela M. McMahon
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Observation is underutilized among men with localized, low-risk prostate cancer. Objective: To assess the costs and benefits of observation versus initial treatment. Design: Decision analysis simulating treatment or observation. Data Sources: Medicare schedules, published literature. Target Population: Men aged 65 and 75 years who had newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 µg/L, stage ≤T2a, Gleason score ≤3 + 3). Time Horizon: Lifetime. Perspective: Societal. Intervention: Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]). Outcome Measures: Quality-adjusted life expectancy and costs. Results of Base-Case Analysis: Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15 374 ($24 520 vs. $39 894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11 746 ($18 302 vs. $30 048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment. Results of Sensitivity Analysis: Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses. Limitation: Results depend on outcomes reported in the published literature, which is limited. Conclusion: Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios. Primary Funding Source: National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Institute for Clinical and Economic Review.
IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis
Authors: A Tefferi, T L Lasho, O Abdel-Wahab, P Guglielmelli, J Patel, D Caramazza, L Pieri, C M Finke, O Kilpivaara, M Wadleigh, M Mai, R F McClure, D G Gilliland, R L Levine, A Pardanani, A M Vannucchi
Journal: Leukemia (2010)

In a multi-institutional collaborative project, 1473 patients with myeloproliferative neoplasms (MPN) were screened for isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations: 594 essential thrombocythemia (ET), 421 polycythemia vera (PV), 312 primary myelofibrosis (PMF), 95 post-PV/ET MF and 51 blast-phase MPN. A total of 38 IDH mutations (18 IDH1-R132, 19 IDH2-R140 and 1 IDH2-R172) were detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, 1 (1%) post-PV/ET MF and 11 (21.6%) blast-phase MPN (P<0.01). Mutant IDH was documented in the presence or absence of JAK2, MPL and TET2 mutations, with similar mutational frequencies. However, IDH-mutated patients were more likely to be nullizygous for JAK2 46/1 haplotype, especially in PMF (P=0.04), and less likely to display complex karyotype, in blast-phase disease (P<0.01). In chronic-phase PMF, JAK2 46/1 haplotype nullizygosity (P<0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7–5.2), but not IDH mutational status (P=0.55; HR 1.3, 95% CI 0.5–3.4), had an adverse effect on survival. This was confirmed by multivariable analysis. In contrast, in both blast-phase PMF (P=0.04) and blast-phase MPN (P=0.01), the presence of an IDH mutation predicted worse survival. The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes.
Maternal HIV Infection and Antibody Responses in Uninfected Infants
Authors: Thais Louvain de Souza, Regina Célia de Souza Campos Fernandes, Enrique Medina-Acosta
Journal: JAMA (2011)

This letter to the editor discusses cases of maternal HIV and the subsequent effect on infants. The letter expresses support for the view that antenatal HIV exposure does not compromise the infant’s ability to respond to vaccines. Some factors that may have influenced supporting studies are breastfeeding a delay in the bacillus Calmette-Gue´rin (BCG) vaccine and a change in the immunization schedule during the study. A response to this letter addressed the potential biases in the research study discussed. The response acknowledges all of these potential biases but asserts that the key point is a demonstrated positive response from the infants in the short term.
Reciprocal Activating Interaction between Natural Killer Cells and Dendritic Cells
Authors: Franca Gerosa, Barbara Baldani-Guerra, Carla Nisii, Viviana Marchesini, Giuseppe Carra, Giorgio Trinchieri
Journal: The Journal of Experimental Medicine (2002)

We analyzed the interaction between human peripheral blood natural killer (NK) cells and monocyte-derived immature dendritic cells (DC). Fresh NK cells were activated, as indicated by the induced expression of the CD69 antigen, and their cytolytic activity was strongly augmented by contact with lipopolysaccharide (LPS)-treated mature DC, or with immature DC in the presence of the maturation stimuli LPS, Mycobacterium tuberculosis or interferon (IFN)-α. Reciprocally, fresh NK cells cultured with immature DC in the presence of the maturation stimuli strongly enhanced DC maturation and interleukin (IL)-12 production. IL-2–activated NK cells directly induced maturation of DC and enhanced their ability to stimulate allogeneic naive CD4+ T cells. The effects of NK cells were cell contact dependent, although the secretion of IFN-γ and TNF also contributed to DC maturation. Within peripheral blood lymphocytes the reciprocal activating interaction with DC was restricted to NK cells, because the other lymphocyte subsets were neither induced to express CD69, nor induced to mature in contact with DC. These data demonstrated for the first time a bidirectional cross talk between NK cells and DC, in which NK cells activated by IL-2 or by mature DC induce DC maturation.
Gastrin inhibits cholangiocarcinoma growth through increased apoptosis by activation of Ca2+-dependent protein kinase C-α
Authors: Noriatsu Kanno, Shannon Glaser, Usha Chowdhury, Jo Lynne Phinizy, Leonardo Baiocchi, Heather Francis, Gene LeSage, Gianfranco Alpini
Journal: Journal of Hepatology (2001)
The usefullness of the chronic obstructive pulmonary disease assessment test
Authors: Young Hwang, Jong Lee, Ho Kim, Ju Cho, You Kim
Journal: European Respiratory Journal (2011)

Background: It is important to assess and monitor the patients in management of COPD. Recently the COPD assessment test (CAT) has been developed as a short simple method for assessing and monitoring of the quality of life in COPD patients. The obsject of this study is to evaluate the usefullness of the Korean version of COPD assessment test (KCAT) for assessing and monitoring COPD patients in Korea.

Methods: The study was included 60 patients with COPD in outpatient clinic. We investigated the frequency of acute exacerbations during a previous year. We also measured the spirometry and distance to walk for 6 minutes and obtained the MMRC dyspnea scale, Korean version of the CAT, and BODE index. To assess the usefulness of KCAT, correlations between KCAT and other methods were evaluated.

Results: The KCAT score was correlated significantly with FEV1% (r=0.323, p=0.012), the frequency of acute exacerbation (r=0.292, p=0.024), MMRC dyspnea scale (r=0.554, p<0.001), BODE index (r=0.380, p=0.003) and 6MWD (r= -0.372, p=0.004). The mean KCAT score was increased according to GOLD stages.

Conclusions: The KCAT were shown to be useful assessment of COPD severity. Therefore the KCAT is easily applicable and simple method for assessment of COPD severity in outpatient clinic in Korea.
EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a task force of ESCISIT
Authors: W Zhang, M Doherty, B F Leeb, L Alekseeva, N K Arden, J W Bijlsma, F Dincer, K Dziedzic, H J Hauselmann, P Kaklamanis, M Kloppenburg, L S Lohmander, E Maheu, E Martin-Mola, K Pavelka, L Punzi, S Reiter, J Smolen, G Verbruggen, I Watt, I Zimmermann-Gorska
Journal: Annals of the Rheumatic Diseases (2008)

To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA).The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale.Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint.Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
The role of the media in the Stoke CNEP Saga
Authors: Jonathan Gornall
Journal: Journal of the Royal Society of Medicine (2010)

As the boxed summary in the first article of this series shows,1 the way the Stoke neonatal CNEP trial was conducted between 1989 and 1993 was investigated 12 times between 1997 and 2008. Much of the public and political concern that led to this activity was generated by a decade of often sensationalist, irresponsible, frequently misleading and inadequately rebutted journalism.
Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95
Authors: CM vanDuijn, N Delasnerie-Laupretre, C Masullo, I Zerr, R de Silva, DPWM Wientjens, J-P Brandel, T Weber, V Bonavita, M Zeidler, A Alperovitch, S Poser, E Granieri, A Hofman, RG Will
Journal: The Lancet (1998)
C. elegans G Protein Regulator RGS-3 Controls Sensitivity to Sensory Stimuli
Authors: Denise M. Ferkey, Rhonda Hyde, Gal Haspel, Heather M. Dionne, Heather A. Hess, Hiroshi Suzuki, William R. Schafer, Michael R. Koelle, Anne C. Hart
Journal: Neuron (2007)
Cardiac CaM Kinase II Genes δ and γ Contribute to Adverse Remodeling but Redundantly Inhibit Calcineurin-Induced Myocardial Hypertrophy
Authors: Michael M. Kreusser, Lorenz H. Lehmann, Stanislav Keranov, Marc-Oscar Hoting, Ulrike Oehl, Michael Kohlhaas, Jan-Christian Reil, Kay Neumann, Michael D. Schneider, Joseph A. Hill, Dobromir Dobrev, Christoph Maack, Lars S. Maier, Hermann-Josef Gröne, Hugo A. Katus, Eric N. Olson, Johannes Backs
Journal: Circulation (2014)

Background— Ca 2+ -dependent signaling through CaM Kinase II (CaMKII) and calcineurin was suggested to contribute to adverse cardiac remodeling. However, the relative importance of CaMKII versus calcineurin for adverse cardiac remodeling remained unclear. Methods and Results— We generated double-knockout mice (DKO) lacking the 2 cardiac CaMKII genes δ and γ specifically in cardiomyocytes. We show that both CaMKII isoforms contribute redundantly to phosphorylation not only of phospholamban, ryanodine receptor 2, and histone deacetylase 4, but also calcineurin. Under baseline conditions, DKO mice are viable and display neither abnormal Ca 2+ handling nor functional and structural changes. On pathological pressure overload and β-adrenergic stimulation, DKO mice are protected against cardiac dysfunction and interstitial fibrosis. But surprisingly and paradoxically, DKO mice develop cardiac hypertrophy driven by excessive activation of endogenous calcineurin, which is associated with a lack of phosphorylation at the auto-inhibitory calcineurin A site Ser411. Likewise, calcineurin inhibition prevents cardiac hypertrophy in DKO. On exercise performance, DKO mice show an exaggeration of cardiac hypertrophy with increased expression of the calcineurin target gene RCAN1-4 but no signs of adverse cardiac remodeling. Conclusions— We established a mouse model in which CaMKII’s activity is specifically and completely abolished. By the use of this model we show that CaMKII induces maladaptive cardiac remodeling while it inhibits calcineurin-dependent hypertrophy. These data suggest inhibition of CaMKII but not calcineurin as a promising approach to attenuate the progression of heart failure.
The Toll-like receptor 2 R753Q polymorphism defines a subgroup of patients with atopic dermatitis having severe phenotype
Authors: Parviz Ahmad-Nejad, Salima Mrabet-Dahbi, Kristine Breuer, Martina Klotz, Thomas Werfel, Udo Herz, Klaus Heeg, Michael Neumaier, Harald Renz
Journal: Journal of Allergy and Clinical Immunology (2004)
Personalized Tamoxifen: A Step Closer but Miles To Go
Authors: Aditya Bardia, Vered Stearns
Journal: Clinical Cancer Research (2010)

Genetic variants in CYP2D6 lead to reduced conversion of tamoxifen to the active metabolite endoxifen. However, the role of the CYP2D6 genotype in predicting tamoxifen-associated outcomes remains controversial. Accurate assignment of the CYP2D6 genotype in archival tissues is crucial for future studies attempting to determine risk prediction of outcomes in tamoxifen-treated individuals.
Serum-free estradiol (E2) levels are prognostic in men with chemotherapy-naive advanced non-small cell lung cancer (NSCLC) and performance status (PS) 2
Authors: H. Ross, F. B. Oldham, B. Bandstra, L. Sandalic, J. Bianco, P. Bonomi, J. W. Singer
Journal: Journal of Clinical Oncology (2007)

7683 Background: In women with advanced NSCLC, premenopausal estradiol levels are associated with a worse survival than postmenopausal levels, suggesting an adverse effect of estradiol on prognosis in NSCLC (JCO 2006, 24(18S):7038; JCO 2006, 24:59–63). Levels of E2, produced from testosterone by aromatase, are often higher in men than in postmenopausal women (Ann Intern Med. 2000, 133:951–63). To investigate the effect of E2 on prognosis in male patients (pts) with advanced NSCLC, total and free E2 levels were assayed in pretreatment samples from men participating in 2 randomized phase III studies, STELLAR 3 and 4. Methods: Free serum E2 levels were measured prior to chemotherapy using a radioimmuno-assay in samples from 289/307 male pts with advanced NSCLC and PS2 enrolled in STELLAR 3 (paclitaxel + carboplatin (C) v. paclitaxel poliglumex (PPX) + C) and STELLAR 4 (vinorelbine or gemcitabine v. PPX). The effect of free E2 levels on survival was evaluated by log rank test. Male pts were categorized as high or low E2 based on values above or below the median (0.42 pg/ml; range: 0.1–2.95).The assay range for normal men is 0.2 - 0.5 pg/ml; in pre- and postmenopausal women, the range is 0.80- 3.45 and 0.12 - 0.39 pg/ml, respectively. Results: Hazard ratio's (HR), median, and 1-yr survival are summarized in the table . Survival was worse for male pts with E2 values higher than the median compared to those below the median (HR 1.56, p = .0008). This difference in survival was not dependent on treatment arm as survival was similar for male pts &gt; 0.42 pg/ml receiving either PPX or control. Conclusions: High serum free E2 levels are associated with shorter survival in men with advanced NSCLC, consistent with the shorter survival noted in NSCLC in premenopausal compared to older women. While PPX is associated with improved survival in women with premenopausal E2 levels (JCO 2006, 24(18S):7039), the relatively low levels of E2 in men may be insufficient to affect survival in male pts receiving PPX. [Table: see text] [Table: see text]