tbuckley/cabot-search huggingface dataset:
The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project)
Authors: Philip S Helliwell, Oliver FitzGerald, Jaap Fransen, Dafna D Gladman, Gerald G Kreuger, Kristina Callis-Duffin, Neil McHugh, Philip J Mease, Vibeke Strand, Robin Waxman, Valderilio Feijo Azevedo, Adriana Beltran Ostos, Sueli Carneiro, Alberto Cauli, Luis R Espinoza, John A Flynn, Nada Hassan, Paul Healy, Eduardo Mario Kerzberg, Yun Jong Lee, Ennio Lubrano, Antonio Marchesoni, Helena Marzo-Ortega, Giovanni Porru, Elvia G Moreta, Peter Nash, Helena Raffayova, Roberto Ranza, Siba P Raychaudhuri, Euthalia Roussou, Raphael Scarpa, Yeong Wook Song, Enrique R Soriano, Paul P Tak, Ilona Ujfalussy, Kurt de Vlam, Jessica A Walsh
Journal: Annals of the Rheumatic Diseases (2012)

Objective To develop new composite disease activity indices for psoriatic arthritis (PsA). Methods Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). Results 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index &gt;10) both nonparametric and AUC curve statistics were nonsignificant for all measures. Conclusions Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.
Stress fracture in long term methotrexate treatment for psoriatic arthritis
Authors: M Wijnands, A Burgers
Journal: Annals of the Rheumatic Diseases (2001)

Case historyA 42 year old woman presented at the outpatient rheumatology department with severe, incapacitating pain of her left leg.There was no previous trauma.The patient did not recall fever or malaise.Psoriasis had been diagnosed at age 17 years.Initially, topical drugs were prescribed.Periodically etretinate, a synthetic analogue of retinoid acid, and photochemotherapy were prescribed as additional treatment.The patient did not receive cyclosporin.Oligoarthritis of her knees and ankles first appeared at an age of 25 years.Management with non-steroidal antiinflammatory drugs and sporadically an intraarticular injection of corticosteroids was adequate to control the symptoms.At age 37 a severe polyarthritis of elbows, wrists, finger joints, ankles, and metatarsophalangeal joints developed.Treatment with methotrexate (MTX) was started at an initial dose of 7.5 mg weekly, resulting in a good clinical response.Two years later the dosage was gradually increased to 20 mg weekly because of a flare.On examination there was little pretibial oedema with tenderness of the distal tibia, especially at the lateral margin.There was an active arthritis of the left knee, wrists, metacarpophalangeal and proximal interphalangeal joints.A cardiorespiratory examination was
micro <scp>RNA</scp> s in psoriasis: leaders or followers?
Authors: J.L.W. Lambert, L. Grine, M. Van Gele
Journal: British Journal of Dermatology (2015)

Journal Article microRNAs in psoriasis: leaders or followers? Get access J.L.W. Lambert, J.L.W. Lambert Department of Dermatology Ghent University Hospital Ghent Belgium Search for other works by this author on: Oxford Academic Google Scholar L. Grine, L. Grine Department of Dermatology Ghent University Hospital Ghent Belgium Search for other works by this author on: Oxford Academic Google Scholar M. Van Gele M. Van Gele Department of Dermatology Ghent University Hospital Ghent Belgium Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 2, 1 August 2015, Page 323, https://doi.org/10.1111/bjd.13837 Published: 01 August 2015
CAT-8015: A Second-Generation<i>Pseudomonas</i>Exotoxin A–Based Immunotherapy Targeting CD22-Expressing Hematologic Malignancies
Authors: Ralph F. Alderson, Robert J. Kreitman, Tianling Chen, Peter Yeung, Ronald Herbst, Judy A. Fox, Ira Pastan
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To compare the in vitro and in vivo efficacy of CAT-8015, a second-generation recombinant immunotoxin composed of disulfide-linked affinity matured VH and VL chains of the mouse anti-CD22 monoclonal antibody RFB4 fused to PE38, to the parental compound CAT-3888. Experimental Design: The biological activity of CAT-8015 was examined in vitro using B-cell tumor lines and in vivo in a JD38-based s.c. tumor model in NCr athymic mice. Pharmacokinetics and interspecies scaling of CAT-8015 were evaluated in mice, rats, and cynomolgus monkeys. The potential toxicity of CAT-8015 was assessed in monkeys in a toxicologic study and compared with CAT-3888. Results: The IC50 values of CAT-8015 in vitro using the EHEB, MEC1, Daudi, CA46, and JD38 cell lines ranged from 0.3 to 8.6 ng/mL. Pharmacokinetic studies with CAT-8015 were conducted in mouse, rat, and cynomolgus monkey. The t1/2 was calculated to be 0.42, 0.61, and 0.79 hours and the Vss was 1.37, 5.57, and 140.3 mL in mouse, rat, and monkey, respectively. In vivo, when JD38 tumor-bearing animals were treated with CAT-8015 at doses ≥75 μg/kg at 48-hour intervals for a total of three doses, a rapid reduction in tumor volume and in some cases complete remission in tumor growth was observed. The comparative toxicologic study showed comparable clinical and anatomic pathology changes for CAT-8015 and CAT-3888. Conclusions: CAT-8015 is a CD22-targeting immunotoxin that, in preclinical studies, has greatly improved efficacy compared with CAT-3888.
Dendritic cell quiescence during systemic inflammation driven by LPS stimulation of radioresistant cells in vivo
Authors: Martijn A. Nolte, Salomé LeibundGut-Landmann, Olivier Joffre, Caetano Reis e Sousa
Journal: The Journal of Experimental Medicine (2007)

Dendritic cell (DC) activation is a prerequisite for T cell priming. During infection, activation can ensue from signaling via pattern-recognition receptors after contact with pathogens or infected cells. Alternatively, it has been proposed that DCs can be activated indirectly by signals produced by infected tissues. To address the contribution of tissue-derived signals, we measured DC activation in a model in which radioresistant cells can or cannot respond to lipopolysaccharide (LPS). We report that recognition of LPS by the radioresistant compartment is sufficient to induce local and systemic inflammation characterized by high circulating levels of tumor necrosis factor (TNF) α, interleukin (IL) 1β, IL-6, and CC chemokine ligand 2. However, this is not sufficient to activate DCs, whether measured by migration, gene expression, phenotypic, or functional criteria, or to render DC refractory to subsequent stimulation with CpG-containing DNA. Similarly, acute or chronic exposure to proinflammatory cytokines such as TNF-α ± interferon α/β has marginal effects on DC phenotype in vivo when compared with LPS. In addition, DC activation and migration induced by LPS is unimpaired when radioresistant cells cannot respond to the stimulus. Thus, inflammatory mediators originating from nonhematopoietic tissues and from radioresistant hematopoietic cells are neither sufficient nor required for DC activation in vivo.
Complexity, connectivity, and duplicability as barriers to lateral gene transfer
Authors: Alon Wellner, Mor N Lurie, Uri Gophna
Journal: Genome biology (2007)

Lateral gene transfer is a major force in microbial evolution and a great source of genetic innovation in prokaryotes. Protein complexity has been claimed to be a barrier for gene transfer, due to either the inability of a new gene's encoded protein to become a subunit of an existing complex (lack of positive selection), or from a harmful effect exerted by the newcomer on native protein assemblages (negative selection). We tested these scenarios using data from the model prokaryote Escherichia coli. Surprisingly, the data did not support an inverse link between membership in protein complexes and gene transfer. As the complexity hypothesis, in its strictest sense, seemed valid only to essential complexes, we broadened its scope to include connectivity in general. Transferred genes are found to be less involved in protein-protein interactions, outside stable complexes, and this is especially true for genes recently transferred to the E. coli genome. Thus, subsequent to transfer, new genes probably integrate slowly into existing protein-interaction networks. We show that a low duplicability of a gene is linked to a lower chance of being horizontally transferred. Notably, many essential genes in E. coli are conserved as singletons across multiple related genomes, have high connectivity and a highly vertical phylogenetic signal. High complexity and connectivity generally do not impede gene transfer. However, essential genes that exhibit low duplicability and high connectivity do exhibit mostly vertical descent.
WNT11 Expression Is Induced by Estrogen-Related Receptor α and β-Catenin and Acts in an Autocrine Manner to Increase Cancer Cell Migration
Authors: Mary A. Dwyer, James D. Joseph, Hilary E. Wade, Matthew L. Eaton, Rebecca S. Kunder, Dmitri Kazmin, Ching-yi Chang, Donald P. McDonnell
Journal: Cancer Research (2010)

Elevated expression of the orphan nuclear receptor estrogen-related receptor α (ERRα) has been associated with a negative outcome in several cancers, although the mechanism(s) by which this receptor influences the pathophysiology of this disease and how its activity is regulated remain unknown. Using a chemical biology approach, it was determined that compounds, previously shown to inhibit canonical Wnt signaling, also inhibited the transcriptional activity of ERRα. The significance of this association was revealed in a series of biochemical and genetic experiments that show that (a) ERRα, β-catenin (β-cat), and lymphoid enhancer-binding factor-1 form macromolecular complexes in cells, (b) ERRα transcriptional activity is enhanced by β-cat expression and vice versa, and (c) there is a high level of overlap among genes previously shown to be regulated by ERRα or β-cat. Furthermore, silencing of ERRα and β-cat expression individually or together dramatically reduced the migratory capacity of breast, prostate, and colon cancer cells in vitro. This increased migration could be attributed to the ERRα/β-cat-dependent induction of WNT11. Specifically, using (a) conditioned medium from cells overexpressing recombinant WNT11 or (b) WNT11 neutralizing antibodies, we were able to show that this protein was the key mediator of the promigratory activities of ERRα/β-cat. Together, these data provide evidence for an autocrine regulatory loop involving transcriptional upregulation of WNT11 by ERRα and β-cat that influences the migratory capacity of cancer cells.
Vitamin D levels in patients with chronic hepatitis B
Authors: Cumali Efe, Tugrul Purnak, Ersan Ozaslan
Journal: Hepatology (2013)

We read with interest the article by Farnik et al.1 regarding the low vitamin D levels in patients with chronic hepatitis B virus (HBV). A remarkable finding was the inverse relationship between serum vitamin D levels and HBV viral load. A previous study in patients with chronic hepatitis C had also shown that necroinflammatory activity as well fibrosis scores were independently linked to low vitamin D levels.2 Because of small cohort size, the researchers could not show an association between serum vitamin D levels and fibrosis scores. However, considering that necroinflammatory activity was not included in statistical analysis in this study; we would like to point out that high necroinflammatory activity may also explain the low vitamin D levels in patients with HBV. Before drawing a definitive conclusion, more details ought to be presented about this important issue. Cumali Efe, M.D.1 Tugrul Purnak, M.D.1 Ersan Ozaslan, M.D.2 1Department of Gastroenterology Hacettepe University Ankara, Turkey 2Department of Gastroenterology Numune Research and Education Hospital Ankara, Turkey
Patterns of evolutionary rate variation among genes of the anthocyanin biosynthetic pathway
Authors: M. D. Rausher, R. E. Miller, P. Tiffin
Journal: Molecular Biology and Evolution (1999)

The anthocyanin biosynthetic pathway is responsible for the production of anthocyanin pigments in plant tissues and shares a number of enzymes with other biochemical pathways. The six core structural genes of this pathway have been cloned and characterized in two taxonomically diverse plant species (maize and snapdragon). We have recently cloned these genes for a third species, the common morning glory, Ipomoea purpurea. This additional information provides an opportunity to examine patterns of evolution among genes within a single biochemical pathway. We report here that upstream genes in the anthocyanin pathway have evolved substantially more slowly than downstream genes and suggest that this difference in evolutionary rates may be explained by upstream genes being more constrained because they participate in several different biochemical pathways. In addition, regulatory genes associated with the anthocyanin pathway tend to evolve more rapidly than the structural genes they regulate, suggesting that adaptive evolution of flower color may be mediated more by regulatory than by structural genes. Finally, for individual anthocyanin genes, we found an absence of rate heterogeneity among three major angiosperm lineages. This rate constancy contrasts with an accelerated rate of evolution of three CHS-like genes in the Ipomoea lineage, indicating that these three genes have diverged without coordinated adjustment by other pathway genes.
Computed tomography assessment of lung volume changes after bronchial valve treatment
Authors: H. O. Coxson, P. V. Nasute Fauerbach, C. Storness-Bliss, N. L. Müller, S. Cogswell, D. H. Dillard, C. L. Finger, S. C. Springmeyer
Journal: European Respiratory Journal (2008)

The aim of the present study was to correlate clinical outcome measures following treatment with bronchial valves with regional lung volume. Computed tomography (CT) scan data from 57 subjects with severe emphysema were obtained from nine North American clinical trial sites. IBV® Valves (Spiration, Inc., Redmond, WA, USA) were placed to occlude segmental and subsegmental bronchi in right and left upper lobes using a flexible bronchoscope. Subjects completed a St George's Respiratory Questionnaire (SGRQ), pulmonary function test (PFT) and exercise capacity test. CT scans were analysed at baseline and at 1, 3 or 6 months after treatment to measure total and lobar lung density, volume and mass. Total lung volumes measured using CT were strongly correlated with PFT and did not change with treatment. However, the treated upper lobes significantly decreased in volume in 88% of the observations, by mean± sd 335±444 mL, or a decrease of 10.2% in the 6 month data. The untreated lobes had an 11.6% increase in volume. Changes in regional lung volume were associated with clinically meaningful improvements in SGRQ (-8.95±16.22), but not clinically meaningful PFT changes. The significant health status improvements reported by subjects following bilateral bronchial valve treatment are associated with regional lung volume changes and interlobar shift measured using computed tomography.
Expression of the Chemokine Monocyte Chemoattractant Protein-1 and Its Receptor Chemokine Receptor 2 in Human Crescentic Glomerulonephritis
Authors: STEPHAN SEGERER, YAN CUI, KELLY L. HUDKINS, TRACY GOODPASTER, FRANK EITNER, MATTHIAS MACK, DETLEF SCHLO[Combining Diaeresis]NDORFF, CHARLES E. ALPERS
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Crescents are morphologic manifestations of severe glomerular injury. Several chemokines and their receptors have been demonstrated to be involved in animal models of crescentic glomerulonephritis (cGN) and are potential targets for therapeutic interventions. Therefore, the expression of monocyte chemoattractant protein-1 (MCP-1), its receptor chemokine receptor 2B (CCR2B), and CCR5 in human cGN was studied. MCP-1 and CCR2B mRNA expression was evaluated, by in situ hybridization, in serial sections of 23 renal biopsies from patients with cGN. T cells, macrophages, and CCR5-expressing cells were examined by immunohistochemical analysis. MCP-1 mRNA was expressed by cells in crescents, parietal epithelium, and tubular epithelium, as well as by infiltrating leukocytes in the tubulointerstitium. The expression of CCR2B mRNA was observed in cells in glomeruli and crescents and in infiltrating leukocytes in the tubulointerstitium. CCR2B mRNA expression could not be clearly localized to intrinsic renal cells; evidence that most of the CCR2B-expressing cells were leukocytes is provided. CD3-positive T cells formed the major part of the interstitial cell infiltrates but were rare within the glomerular tufts. CD68-positive macrophages constituted a major population of infiltrating cells in crescents and contributed significantly to the interstitial infiltrates. The number of glomerular macrophages was associated with the number of MCP-1- and CCR2B-positive glomerular cells. Expression of CCR2B was significantly correlated with interstitial CD3-positive T cells. CCR5 expression was restricted to infiltrating leukocytes and was correlated quantitatively and by localization with interstitial CD3-positive T cells and CD68-positive macrophages. These first morphologic data on the distribution of CCR2-positive cells in human cGN suggest differential effects of chemokines and their receptors on the distribution of infiltrating leukocytes in different compartments of the kidney.
Suppression of Demand Pacemakers by Inactive Pacemaker Electrodes
Authors: WARREN D. WIDMANN, STELIO MANGIOLA, LAWRENCE A. LUBOW, FAYETTA M. DOLAN
Journal: Circulation (1972)

Ventricular inhibited cardiac pacemakers were suppressed by intimate contact of the tip of the active pacemaker electrode with that of the inactive pacemaker electrode in two patients. This contact apparently was sensed as myocardial electrical activity and resulted in variable suppression of pacemaker emission. There was no interference with R-wave sensing function. The threshold for stimulation was unaffected. There was no loss of capture as tested with the magnet-controlled continuous mode of stimulation. This type of pacemaker failure can be remedied simply by withdrawing the tips of the electrodes from intimate contact.
Transmural Extent of Acute Myocardial Infarction Predicts Long-Term Improvement in Contractile Function
Authors: Kelly M. Choi, Raymond J. Kim, George Gubernikoff, John D. Vargas, Michelle Parker, Robert M. Judd
Journal: Circulation (2001)

Previous animal studies have demonstrated that the transmural extent of acute myocardial infarction defined by contrast-enhanced MRI (ceMRI) relates to early restoration of flow and future improvements in contractile function. We tested the hypothesis that ceMRI would have similar predictive value in humans.Twenty-four patients who presented with their first myocardial infarction and were successfully revascularized underwent cine and ceMRI of their heart within 7 days (scan 1) of the peak MB band of creatine kinase. Cine MRI was repeated 8 to 12 weeks later (scan 2). The transmural extent of infarction on scan 1 and wall thickening on both scans were determined using a 72-segment model. A total of 524 of 1571 segments (33%) were dysfunctional on scan 1. Improvement in segmental contractile function on scan 2 was inversely related to the transmural extent of infarction on scan 1 (P=0.001). Improvement in global contractile function, as assessed by ejection fraction and mean wall thickening score, was not predicted by peak creatine kinase-MB (P=0.66) or by total infarct size, as defined by MRI (P=0.70). The best predictor of global improvement was the extent of dysfunctional myocardium that was not infarcted or had infarction comprising <25% of left ventricular wall thickness (P<0.005 for ejection fraction, P<0.001 for mean wall thickening score).In patients with acute myocardial infarction, the transmural extent of infarction defined by ceMRI predicts improvement in contractile function.
Toxicity and Antitumor Activity of Gallium Nitrate and Periodically Related Metal Salts2&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Michael M. Hart, Clara F. Smith, Sidney T. Yancey, Richard H. Adamson
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Toxicity and Antitumor Activity of Gallium Nitrate and Periodically Related Metal Salts2 Get access Michael M. Hart, Michael M. Hart Laboratory of Chemical Pharmacology, National Cancer Institute,6Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Clara F. Smith, Clara F. Smith Laboratory of Chemical Pharmacology, National Cancer Institute,6Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sidney T. Yancey, Sidney T. Yancey Laboratory of Chemical Pharmacology, National Cancer Institute,6Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard H. Adamson Richard H. Adamson 5 Laboratory of Chemical Pharmacology, National Cancer Institute,6Bethesda, Maryland 20014 5Address reprint requests to: Dr. R. H. Adamson, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 5, November 1971, Pages 1121–1128, https://doi.org/10.1093/jnci/47.5.1121 Published: 01 November 1971 Article history Received: 16 June 1971 Accepted: 30 July 1971 Published: 01 November 1971
GP fails in attempt to reverse decision to suspend his practice
Authors: C. Dyer
Journal: BMJ (2015)

The Care Standards Tribunal of England and Wales has upheld the first decision by the healthcare regulator the Care Quality Commission (CQC) to suspend a general practice from providing services.

The regulator suspended the south London practice of Mujib ul Haq Khan for four months in January 2015 after “serious concerns about patient safety,” in the first use of this enforcement power against a GP. NHS England temporarily distributed the 790 patients of the Granville Road Surgery in Southfields among other local practices.

The tribunal’s jurisdiction covers appeals against a wide range of decisions on registration in the health, education, and social care fields, including decisions …