tbuckley/cabot-search huggingface dataset:
Phase II Study of Androgen Synthesis Inhibition with Ketoconazole, Hydrocortisone, and Dutasteride in Asymptomatic Castration-Resistant Prostate Cancer
Authors: Mary-Ellen Taplin, Meredith M. Regan, Yoo-Joung Ko, Glenn J. Bubley, Stephen E. Duggan, Lillian Werner, Tomasz M. Beer, Christopher W. Ryan, Paul Mathew, Shi-Ming Tu, Samuel R. Denmeade, William K. Oh, Oliver Sartor, Christos S. Mantzoros, Roger Rittmaster, Philip W. Kantoff, Steven P. Balk
Journal: Clinical Cancer Research (2009)

Increasing evidence indicates that enhanced intratumoral androgen synthesis contributes to prostate cancer progression after androgen deprivation therapy. This phase II study was designed to assess responses to blocking multiple steps in androgen synthesis with inhibitors of CYP17A1 (ketoconazole) and type I and II 5alpha-reductases (dutasteride) in patients with castration-resistant prostate cancer (CRPC).Fifty-seven men with CRPC were continued on gonadal suppression and treated with ketoconazole (400 mg thrice daily), hydrocortisone (30 mg/AM, 10 mg/PM), and dutasteride (0.5 mg/d).Prostate-specific antigen response rate (> or =50% decline) was 56% (32 of 57; 95% confidence interval, 42.4-69.3%); the median duration of response was 20 months. In patients with measurable disease, 6 of 20 (30%) responded by the Response Evaluation Criteria in Solid Tumors. Median duration of treatment was 8 months; 9 patients remained on therapy with treatment durations censored at 18 to 32 months. Median time to progression was 14.5 months. Grade 3 toxicities occurred in 32% with only one reported grade 4 (thrombosis) toxicity. Dehydroepiandrosterone sulfate declined by 89%, androstenedione by 56%, and testosterone by 66%, and dihydrotestosterone declined to below detectable levels compared with baseline levels with testicular suppression alone. Median baseline levels and declines in dehydroepiandrosterone sulfate, androstenedione, testosterone, and dihydrotestosterone were not statistically different in the responders versus nonresponders, and hormone levels were not significantly increased from nadir levels at relapse.The response proportion to ketoconazole, hydrocortisone, and dutasteride was at least comparable with previous studies of ketoconazole alone, whereas time to progression was substantially longer. Combination therapies targeting multiple steps in androgen synthesis warrant further investigation.
Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma
Authors: J. C. Ho, M. Chan-Yeung, S. P. Ho, J. C. Mak, M. S. Ip, G. C. Ooi, M. P. Wong, K. W. Tsang, W. K. Lam
Journal: European Respiratory Journal (2006)

The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2 (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.
Extremity magnetic resonance imaging assessment of synovitis (without contrast) in rheumatoid arthritis may be less accurate than power Doppler ultrasound
Authors: J E Freeston, A K Brown, E M A Hensor, P Emery, P G Conaghan
Journal: Annals of the Rheumatic Diseases (2007)

Although synovitis detection is optimal with contrast-enhanced, high field magnetic resonance imaging (MRI), the increased accessibility of power Doppler ultrasound (PDUS) has meant that it is more frequently utilised in the clinical setting. However, with the advent of low field extremity MRI (eMRI) and its practical advantages,1 there is a need to understand what is the most sensitive tool for routine clinical use. eMRI has been evaluated with respect to its ability to assess rheumatoid arthritis erosions in comparison with both high field MRI and radiography.2–4 There is relatively little published work, however, on eMRI’s ability to assess synovitis in comparison with high field MRI,4–7 and three of these reports used intravenous contrast, which further limits feasibility. Only one group have published …
Bcl6 expression specifies the T follicular helper cell program in vivo
Authors: Xindong Liu, Xiaowei Yan, Bo Zhong, Roza I. Nurieva, Aibo Wang, Xiaohu Wang, Natalia Martin-Orozco, Yihong Wang, Seon Hee Chang, Enric Esplugues, Richard A. Flavell, Qiang Tian, Chen Dong
Journal: The Journal of Experimental Medicine (2012)

T follicular helper cells (Tfh cells) play a pivotal role in germinal center reactions, which require B cell lymphoma 6 (Bcl6) transcription factor. To analyze their relationships with other effector T cell lineages and their stability in vivo, we developed and analyzed a new Bcl6 reporter mouse alone or together with other lineage reporter systems. Assisted with genome-wide transcriptome analysis, we show substantial plasticity of T cell differentiation in the early phase of immune response. At this stage, CXCR5 appears to be expressed in a Bcl6-independent manner. Once Bcl6 is highly expressed, Tfh cells can persist in vivo and some of them develop into memory cells. Together, our results indicate Bcl6 as a bona fide marker for Tfh polarized program.
Immunosurveillance and Survivin-Specific T-Cell Immunity in Children With High-Risk Neuroblastoma
Authors: Christina M. Coughlin, Mark D. Fleming, Richard G. Carroll, Bruce R. Pawel, Michael D. Hogarty, Xiaochuan Shan, Barbara A. Vance, Jarish N. Cohen, Sonya Jairaj, Elaina M. Lord, Michael H. Wexler, Gwenn-aël H. Danet-Desnoyers, Jack L. Pinkus, Geraldine S. Pinkus, John M. Maris, Stephan A. Grupp, Robert H. Vonderheide
Journal: Journal of Clinical Oncology (2006)

Purpose Tumor immunosurveillance influences oncogenesis and tumor growth, but it remains controversial whether clinical failure of immunosurveillance is a result of lymphocyte dysfunction or tumor escape. In this study, our goal was to characterize the physiology of tumor immunosurveillance in children with high-risk neuroblastoma (HR-NBL). Patients and Methods Immunohistopathologic studies were carried out on 26 tumor samples from a cohort of HR-NBL patients diagnosed at Children's Hospital of Philadelphia for the 2-year period from May 2003 to May 2005. Blood from nine HLA-A2 + patients in this cohort was analyzed for T cells specific for the antiapoptotic protein survivin. Results Survivin protein was expressed by 26 of 26 tumors. In HLA-A2 + patients, circulating cytotoxic T lymphocytes (CTLs) specific for survivin were detected by peptide/major histocompatibility complex tetramer analysis in the blood of eight of nine children with HR-NBL at the time of diagnosis. Rather than being selectively rendered anergic in vivo, circulating survivin-specific CTLs were highly functional as shown by cytotoxicity and interferon gamma enzyme-linked immunospot assays in six of nine patients. Survivin-specific CD107a mobilization by T cells was found in five of five patients. By immunohistochemistry, tumor-infiltrating T cells were few or absent in 26 of 26 tumors. Conclusion Children with HR-NBL harbor robust cellular immune responses to the universal tumor antigen survivin at the time of diagnosis, but intratumoral T cells are strikingly rare, suggesting a failure of cellular immunosurveillance. Efforts to develop novel therapies that increase T-cell trafficking into tumor nests are warranted.
Resequencing of the CETP gene in American whites and African blacks: Association of rare and common variants with HDL-cholesterol levels
Authors: Dilek Pirim, Xingbin Wang, Vipavee Niemsiri, Zaheda H. Radwan, Clareann H. Bunker, John E. Hokanson, Richard F. Hamman, M. Michael Barmada, F. Yesim Demirci, M. Ilyas Kamboh
Journal: Metabolism (2015)
Aryl hydrocarbon receptor antagonism mitigates cytokine-mediated inflammatory signalling in primary human fibroblast-like synoviocytes
Authors: Tejas S Lahoti, Kaarthik John, Jarod M Hughes, Ann Kusnadi, Iain A Murray, Gowdahalli Krishnegowda, Shantu Amin, Gary H Perdew
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Rheumatoid Arthritis (RA) is a chronic inflammatory disease of unclear aetiology, which is associated with inflamed human fibroblast-like synoviocytes (HFLS). Epidemiological studies have identified a positive correlation between tobacco smoking (a rich source of aryl hydrocarbon receptor (AHR) agonists) and aggressive RA phenotype. Thus, we hypothesise that antagonism of AHR activity by a potent AHR antagonist GNF351 can attenuate the inflammatory phenotype of HFLS-RA cells. <h3>Methods</h3> Quantitative PCR was used to examine IL1B-induced mRNA expression in primary HFLS-RA cells. A structurally diverse AHR antagonist CH223191 and transient AHR repression using AHR small interfering RNA (siRNA) in primary HFLS-RA cells were used to demonstrate that effects observed by GNF351 are AHR-mediated. The levels of PTGS2 were determined by western blot and secretory cytokines such as IL1B and IL6 by ELISA. Chromatin-immunoprecipitation was used to assess occupancy of the AHR on the promoters of <i>IL1B</i> and <i>IL6</i>. <h3>Results</h3> Many of the chemokine and cytokine genes induced by IL1B in HFLS-RA cells are repressed by co-treatment with GNF351 at both the mRNA and protein level. Pretreatment of HLFS-RA cells with CH223191 or transient gene ablation of AHR by siRNA confirmed that the effects of GNF351 are AHR-mediated. GNF351 inhibited the recruitment of AHR to the promoters of <i>IL1B</i> and <i>IL6</i> confirming occupancy of AHR at these promoters is required for enhanced inflammatory signalling. <h3>Conclusions</h3> These data suggest that AHR antagonism may represent a viable adjuvant therapeutic strategy for the amelioration of inflammation associated with RA.
Effect of tibial positioning on the diagnosis of posterolateral rotatory instability in the posterior cruciate ligament-deficient knee
Authors: Eric J Strauss, Charbel Ishak, Christopher Inzerillo, Michael Walsh, Gokce Yildirim, Peter Walker, Laith Jazrawi, Jeffrey Rosen
Journal: British Journal of Sports Medicine (2007)

Objective: To determine whether positioning of the tibia affects the degree of tibial external rotation seen during a dial test in the posterior cruciate ligament (PCL)–posterolateral corner (PLC)-deficient knee. Design: Laboratory investigation. Setting: Biomechanics laboratory. Hypothesis: An anterior force applied to the tibia in the combined PCL–PLC-deficient knee will yield increased tibial external rotation during a dial test. Methods: The degree of tibial external rotation was measured with 5 N⋅m of external rotation torque applied to the tibia at both 30° and 90° of knee flexion. Before the torque was applied, an anterior force, a posterior force, or neutral (normal, reduced control) force was applied to the tibia. External rotation measurements were repeated after sequential sectioning of the PCL, the posterolateral structures and the fibular collateral ligament (FCL). Results: Baseline testing of the intact specimens demonstrated a mean external rotation of 18.6° with the knee flexed to 30° (range 16.1–21.0°), and a mean external rotation of 17.3° with the knee flexed to 90° (range 13.8–20.0°). Sequential sectioning of the PCL, popliteus and popliteofibular ligament, and the FCL led to a significant increase in tibial external rotation compared with the intact knee for all testing scenarios. After sectioning of the popliteus and popliteofibular ligament, the application of an anterior force during testing led to a mean tibial external rotation that was 5° greater than during testing in the neutral position and 7.5° greater than during testing with a posterior force. In the PCL, popliteus/popliteofibular ligament and FCL-deficient knee, external rotation was 9° and 12° greater with the application of an anterior force during testing compared with neutral positioning and the application of a posterior force, respectively. Conclusion: An anterior force applied to the tibia during the dial test in a combined PCL–PLC-injured knee increased the overall amount of observed tibial external rotation during the dial test. The anterior force reduced the posterior tibial subluxation associated with PCL injury, which is analogous to what is observed when the dial test is performed with the patient in the prone position. Reducing the tibia with either an anterior force when the patient is supine or performing the dial test with the patient in the prone position increases the ability of an examiner to detect a concomitant PLC injury in the setting of a PCL-deficient knee.
Localized reentry. Mechanism of induced sustained ventricular tachycardia in canine model of recent myocardial infarction.
Authors: H Garan, J N Ruskin
Journal: Journal of Clinical Investigation (1984)

This study was undertaken to investigate the mechanism underlying sustained monomorphic ventricular tachycardia (VT) in late experimental canine myocardial infarction. The hypothesis that sustained and "organized" continuous electrical activity (CEA) displaying a reproducible pattern with recurrent components recorded by bipolar endocardial, intramural, or epicardial electrodes in 10 animals during electrically induced sustained monomorphic VT represented reentrant excitation in an anatomically small area of the ventricle, was evaluated in the light of the following observations: Organized CEA always preceded the first monomorphic ventricular complex (QRS) of VT as well as the discrete local electrograms from closely surrounding sites during the initiation of VT. The site of organized CEA corresponded to the site of origin of sustained VT determined by iso-chronous contour map analysis of activation sequence. Ventricular pacing at rates more rapid than that of VT failed to terminate VT despite ventricular capture unless it transformed CEA into discrete local electrograms. VT could be terminated in three animals, with a single, critically timed premature stimulus delivered at a critically located focus close to the site of CEA, which would result in local capture and interrupted CEA. In six animals, surgical ablation of the site of organized CEA effectively prevented the reinitiation of sustained VT by programmed cardiac stimulation. These data showed that organized CEA and sustained VT were closely associated phenomena and suggested that organized CEA probably represented an important component of the tachycardia circuit.
Why use theories in qualitative research?
Authors: S. Reeves, M. Albert, A. Kuper, B. D. Hodges
Journal: BMJ (2008)

<h3>Abstract</h3> Phosphate acquisition by plants is an essential process that is directly implicated in the optimization of crop yields. Purple acid phosphatases (PAPs) are ubiquitous metalloenzymes, which catalyze the hydrolysis of a wide range of phosphate esters and anhydrides. While some plant PAPs display a preference for ATP as the substrate, others are efficient in hydrolyzing phytate or 2-phosphoenolpyruvate (PEP). PAP from red kidney bean (rkbPAP) is an efficient ATP- and ADPase, but has no activity towards phytate. The crystal structure of this enzyme in complex with an ATP analogue (to 2.20 Å resolution) provides insight into the amino acid residues that play an essential role in binding this substrate. Homology modelling was used to generate three-dimensional structures for the active sites of PAPs from tobacco (NtPAP) and <i>Arabidopsis thaliana</i> (AtPAP12 and AtPAP26) that are efficient in hydrolyzing phytate and PEP as substrates, respectively. In combination with substrate docking simulations and a phylogenetic analysis of 49 plant PAP sequences (including the first PAP sequences reported from <i>Eucalyptus</i>), several active site residues were identified that are important in defining the substrate specificities of plant PAPs. These results may inform bioengineering studies aimed at identifying and incorporating suitable plant PAP genes into crops to improve phosphorus use efficiency. Organic phosphorus sources increasingly supplement or replace inorganic fertilizer, and efficient phosphorus use of crops will lower the environmental footprint of agriculture while enhancing food production.
A NOVEL METHOD FOR SEPTAL ABLATION: GLUE (CYANOACRYLATE) SEPTAL ABLATION
Authors: Ali Oto, Kudret Aytemir, Sercan Okutucu, Ergün B. Kaya, Barbaros Çil, Ali Deniz, Hikmet Yorgun, Onur S. Deveci, Hakan Aksoy, Giray Kabakçi, Nasi Nazli, Hilmi özkutlu
Journal: Journal of the American College of Cardiology (2010)
Sibling Recurrence and the Genetic Epidemiology of Autism
Authors: John N. Constantino, Yi Zhang, Thomas Frazier, Anna M. Abbacchi, Paul Law
Journal: American Journal of Psychiatry (2010)

Objective: Although the symptoms of autism exhibit quantitative distributions in nature, estimates of recurrence risk in families have never previously considered or incorporated quantitative characterization of the autistic phenotype among siblings. Method: The authors report the results of quantitative characterization of 2,920 children from 1,235 families participating in a national volunteer register, with at least one child clinically affected by an autism spectrum disorder and at least one full biological sibling. Results: A traditionally defined autism spectrum disorder in an additional child occurred in 10.9% of the families. An additional 20% of nonautism-affected siblings had a history of language delay, one-half of whom exhibited autistic qualities of speech. Quantitative characterization using the Social Responsiveness Scale supported previously reported aggregation of a wide range of subclinical (quantitative) autistic traits among otherwise unaffected children in multiple-incidence families and a relative absence of quantitative autistic traits among siblings in single-incidence families. Girls whose standardized severity ratings fell above a first percentile severity threshold (relative to the general population distribution) were significantly less likely to have elicited community diagnoses than their male counterparts. Conclusions: These data suggest that, depending on how it is defined, sibling recurrence in autism spectrum disorder may exceed previously published estimates and varies as a function of family type. The results support differences in mechanisms of genetic transmission between simplex and multiplex autism and advance current understanding of the genetic epidemiology of autism spectrum conditions.
Contact dermatitis and quality of life: a structured review of the literature
Authors: R. Skoet, R. Zachariae, T. Agner
Journal: British Journal of Dermatology (2003)

Quality of life (QoL) assessment has rapidly become an important outcome variable in dermatology research. Even though the importance of the patient's personal morbidity is generally accepted as being important by dermatologists, scepticism and confusion remain about the usefulness of QoL in dermatological research and how it should be measured. QoL assessments in individuals with contact dermatitis are few. A structured review of the literature is presented. All studies reviewed found that contact dermatitis is associated with impaired health-related QoL. Hand eczema appears to be as equally impairing as generalized eczema and an early, confirmed diagnosis is associated with improved QoL. Disease duration, atopic dermatitis, age and gender do not seem to have a major impact on QoL, although contradictory findings exist. Assessment of QoL in contact dermatitis is required for future clinical research and may be a valuable tool to the clinician to evaluate new treatments. A combination of dermatology-specific (e.g. Dermatology Life Quality Index) and generic questionnaires (e.g. the Short Form-36) is supported.
A disc diffusion assay for detection of class A, B and OXA-48 carbapenemases in Enterobacteriaceae using phenyl boronic acid, dipicolinic acid and temocillin
Authors: K. van Dijk, G.M. Voets, J. Scharringa, S. Voskuil, A.C. Fluit, W.C. Rottier, M.A. Leverstein-Van Hall, J. W. T. Cohen Stuart
Journal: Clinical Microbiology and Infection (2013)
18F-Fluoro-deoxy-glucose positron emission tomography in lymphoma of mucosa-associated lymphoid tissue: histology makes the difference
Authors: M. Hoffmann, S. Wöhrer, A. Becherer, A. Chott, B. Streubel, K. Kletter, M. Raderer
Journal: Annals of Oncology (2006)

The usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose Positron emission tomography (18F-FDG-PET) in lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is still a matter of debate, and conflicting results have been reported. We have evaluated whether the histological feature of plasmacytic differentiation (PD) might explain the heterogeneous behavior of MALT lymphoma regarding 18F-FDG uptake.A total of 35 patients with a diagnosis of MALT lymphoma referred to our PET unit were studied. Whole-body 18F-FDG-PET scans were carried out on a General Electrics advanced PET scanner 40 min after i.v. injection of 300-380 MBq 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake, standard uptake values (SUVs) were calculated.A total of 19 patients had MALT lymphoma with plasmacytic differentiation (pMALT), while MALT lymphoma without plasmacytic features was diagnosed in 16 patients. Sixteen of 19 patients with PD showed significant 18F-FDG uptake in involved sites (SUV: 3.5-11.7). By contrast, 13 of 16 patients with normal MALT lymphoma showed a false-negative 18F-FDG-PET result. Two of these patients disclosed no tracer uptake in the majority of involved sites apart from one single lesions, while three had a true-positive 18F-FDG-PET scan (SUV: 3.4-6.0).18F-FDG-PET visualizes pMALT in a high proportion of patients, whereas FDG-PET results are significantly less reliable in typical MALT (P = 0.001). This finding may partly account for the heterogeneous results of 18F-FDG-PET-studies in MALT lymphoma.