tbuckley/cabot-search huggingface dataset:
How not to miss autoinflammatory diseases masquerading as urticaria
Authors: K. Krause, C. E. Grattan, C. Bindslev‐Jensen, M. Gattorno, T. Kallinich, H. D. de Koning, H. J. Lachmann, D. Lipsker, A. A. Navarini, A. Simon, C. Traidl‐Hoffmann, M. Maurer
Journal: Allergy (2012)

Urticarial skin reactions are one of the most frequent problems seen by allergists and clinical immunologists in daily practice. The most common reason for recurrent wheals is spontaneous urticaria. There are, however, several less common diseases that present with urticarial rash, such as urticarial vasculitis and autoinflammatory disorders. The latter include cryopyrin-associated periodic syndrome and Schnitzler's syndrome, both rare and disabling conditions mediated by increased interleukin-1 secretion. Apart from the urticarial rash, patients are suffering from a variety of systemic symptoms including recurrent fever attacks, arthralgia or arthritis and fatigue. Autoinflammatory diseases are often associated with a diagnostic delay of many years and do not respond to antihistamines and other treatments of urticaria. Also, the chronic inflammation may lead to long-term complications such as amyloidosis. It is therefore important not to miss these diseases when diagnosing and treating patients with chronic recurrent urticarial rash. Here, we present clinical clues and tips that can help to identify autoinflammatory disorders in patients presenting with chronic urticarial rash and discuss their clinical picture and management.
Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues.
Authors: Yan Zhang, Hector Romero, Gustavo Salinas, Vadim N Gladyshev
Journal: Genome biology (2006)

Abstract Background Selenocysteine (Sec) is co-translationally inserted into protein in response to UGA codons. It occurs in oxidoreductase active sites and often is catalytically superior to cysteine (Cys). However, Sec is used very selectively in proteins and organisms. The wide distribution of Sec and its restricted use have not been explained. Results We conducted comparative genomics and phylogenetic analyses to examine dynamics of Sec decoding in bacteria at both selenium utilization trait and selenoproteome levels. These searches revealed that 21.5% of sequenced bacteria utilize Sec, their selenoproteomes have 1 to 31 selenoproteins, and selenoprotein-rich organisms are mostly Deltaproteobacteria or Firmicutes / Clostridia . Evolutionary histories of selenoproteins suggest that Cys-to-Sec replacement is a general trend for most selenoproteins. In contrast, only a small number of Sec-to-Cys replacements were detected, and these were mostly restricted to formate dehydrogenase and selenophosphate synthetase families. In addition, specific selenoprotein gene losses were observed in many sister genomes. Thus, the Sec/Cys replacements were mostly unidirectional, and increased utilization of Sec by existing protein families was counterbalanced by loss of selenoprotein genes or entire selenoproteomes. Lateral transfers of the Sec trait were an additional factor, and we describe the first example of selenoprotein gene transfer between archaea and bacteria. Finally, oxygen requirement and optimal growth temperature were identified as environmental factors that correlate with changes in Sec utilization. Conclusion Our data reveal a dynamic balance between selenoprotein origin and loss, and may account for the discrepancy between catalytic advantages provided by Sec and the observed low number of selenoprotein families and Sec-utilizing organisms.
954 DIFFERENT MANIFESTATIONS OF CHOLESTATIC COMPLICATIONS IN SEPTICEMIC ICU-PATIENTS: SECONDARY SCLEROSING CHOLANGITIS VERSUS NON-OBSTRUCTIVE CHOLESTASIS
Authors: G. Kirchner, P. Ruemmele, M. Wimmer, B. Goehlmann, J. Hartl, J. Langgartner, C. Gelbmann
Journal: Journal of Hepatology (2012)
Bats with hATs: Evidence for Recent DNA Transposon Activity in Genus Myotis
Authors: D. A. Ray, H. J. T. Pagan, M. L. Thompson, R. D. Stevens
Journal: Molecular Biology and Evolution (2006)

Transposable elements make up a significant fraction of many eukaryotic genomes. Although both classes of transposable elements, the DNA transposons and the retrotransposons, show substantial expansion in plants and invertebrates, the DNA transposons are thought to have become inactive in mammalian genomes long ago. Here, we report the first evidence for recent activity of DNA transposons in a mammalian lineage, the bat genus Myotis. Six recently active families of nonautonomous hobo/Activator/TAM transposons were identified in the Myotis lucifugus genome using computational tools. Low sequence divergence among the individual sequences and between individual sequences and their respective consensus sequences suggest their recent expansion in the M. lucifugus genome. Furthermore, amplification and sequencing of polymorphic insertion loci in a related taxon, M. austroriparius, confirms their recent activity. Myotis is one of the largest mammalian genera with 103 species. The discovery of DNA transposon activity in this genus may therefore influence our understanding of genome evolution and diversification in bats and in mammals in general. Furthermore, the identification of a likely autonomous element may lead to new approaches for mammalian genetic manipulation.
ABC of rheumatology
Authors: Y SHOENFELD
Journal: Annals of the Rheumatic Diseases (2001)

ABC of rheumatology . Michael L Snaith. (Pp 90; £17.95.) London: BMJ Publishing Group, 1999. ISBN 0-7279-1385-9.

The name of the book represents its content. It is aimed at students, internists, and general practitioners, yet young …
Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial
Authors: Thomas P Leist, Giancarlo Comi, Bruce A C Cree, Patricia K Coyle, Mark S Freedman, Hans-Peter Hartung, Patrick Vermersch, Florence Casset-Semanaz, Matthew Scaramozza
Journal: The Lancet Neurology (2014)
High-Density Lipoprotein Cholesterol, Size, Particle Number, and Residual Vascular Risk After Potent Statin Therapy
Authors: Samia Mora, Robert J. Glynn, Paul M Ridker
Journal: Circulation (2013)

Background— Chemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy. Methods and Results— In Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/d or placebo. Levels were examined with first CVD (n=234). HDL-P correlated better with apoA-I (Spearman r =0.69, P &lt;0.0001) than with HDL-C ( r =0.55, P &lt;0.0001). Rosuvastatin lowered low-density lipoprotein cholesterol (49%) and raised HDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%), and HDL size (1.2%); all P &lt;0.0001. Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor–adjusted hazard ratio and 95% confidence interval per 1 standard deviation: 0.79 [0.63–0.98], 0.75 [0.62–0.92], and 0.81 [0.67–0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57–0.93, P =0.01) than HDL-C (0.82, 0.63–1.08, P =0.16) or apoA-I (0.86, 0.67–1.10, P =0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53–0.97, P =0.03) after additionally adjusting for HDL-C. In risk factor–adjusted models, HDL size showed no significant association with CVD. Conclusions— In the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.
Extramedullary relapse in acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy
Authors: S de Botton, M A Sanz, S Chevret, H Dombret, G Martin, X Thomas, J D Mediavilla, C Recher, L Ades, B Quesnel, P Brault, M Fey, H Wandt, D Machover, A Guerci, F Maloisel, A M Stoppa, C Rayon, J M Ribera, C Chomienne, L Degos, P Fenaux
Journal: Leukemia (2005)
Pulmonary Function after Exposure to the World Trade Center Collapse in the New York City Fire Department
Authors: Gisela I. Banauch, Charles Hall, Michael Weiden, Hillel W. Cohen, Thomas K. Aldrich, Vasillios Christodoulou, Nicole Arcentales, Kerry J. Kelly, David J. Prezant
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

On September 11, 2001, the World Trade Center collapse created an enormous urban disaster site with high levels of airborne pollutants. First responders, rescue and recovery workers, and residents have since reported respiratory symptoms and developed pulmonary function abnormalities.To quantify respiratory health effects of World Trade Center exposure in the New York City Fire Department.Longitudinal study of pulmonary function in 12,079 New York City Fire Department rescue workers employed on or before 09/11/2001. Between 01/01/1997 and 09/11/2002, 31,994 spirometries were obtained and the FEV(1) and FVC were analyzed for differences according to estimated World Trade Center exposure intensity. Adjusted average FEV(1) during the first year after 09/11/2001 was compared with the 5 yr before 09/11/2001. Median time between 09/11/2001 and a worker's first spirometry afterwards was 3 mo; 90% were assessed within 5 mo.World Trade Center-exposed workers experienced a substantial reduction in adjusted average FEV(1) during the year after 09/11/2001 (372 ml; 95% confidence interval, 364-381 ml; p < 0.001) This exposure-related FEV(1) decrement equaled 12 yr of aging-related FEV(1) decline. Moreover, exposure intensity assessed by initial arrival time at the World Trade Center site correlated linearly with FEV(1) reduction in an exposure intensity-response gradient (p = 0.048). Respiratory symptoms also predicted a further FEV(1) decrease (p < 0.001). Similar findings were observed for adjusted average FVC.World Trade Center exposure produced a substantial reduction in pulmonary function in New York City Fire Department rescue workers during the first year after 09/11/2001.
CHRONIC DISTAL BICEPS TENDON RUPTURE: RETROSPECTIVE REVIEW OF OUTOCOMES OF A NOVEL TECHNIQUE OF RECONSTRUCTION WITH TENDON GRAFT
Authors: T Goetz, M Okada, A Scott, J Pike
Journal: British Journal of Sports Medicine (2013)

Introduction The biceps brachii muscle is the primary forearm supinator and a secondary elbow flexor. The pathophysiology of distal tendon ruptures is still unclear. Patients with chronic rupture presenting 4–6 weeks after the original injury often due to mis-diagnosis or neglect have been, until recently treated non-operatively. The chronic case of biceps tendon rupture poses a surgical challenge due the retraction of the muscle and scarring or resorption of the tendon that may make it impossible to reattach primarily. A novel technique of reconstruction using tendon graft has been developed by the author. The study aims to measure subjective and objective outcomes of reconstruction with this technique. Methods This is a retrospective review of nine patients (mean age 47±10) treated with tendon reconstruction an average of 17 months following injury. Patients were evaluated and graded for bicep contour, range of motion, Mayo Elbow Performance Index (MEPI) and for bilateral elbow flexion and supination torque on a Biodex System 4 Pro dynamometer. Patient reported outcome questionnaires were also collected. Results The mean Disabilities of the Arm, Shoulder, and Hand score (DASH), American Shoulder and Elbow Society score (ASES), and Mayo Elbow Performance Index (MEPI) were 11±10, 91±10, and 88±14 respectively. Eighty of nine subjects were somewhat or very satisfied with the reconstruction. Biceps contour was 4.7 cm above the antecubital fossa on the operative side versus 3.9 cm on the nonoperative side. No statistically different strength discrepancies were noted between the operative and nonoperative sides when comparing isometric supination strength (p=0.42) and flexion strength (p=0.17), as well as peak supination torque at 90 degrees of elbow flexion (p=0.09). Discussion Reconstruction of chronic distal biceps tendon rupture with tendon graft resulted in low patient-reported disability and high patient satisfaction. No statistically different values in isokinetic supination and elbow flexion strength were noted between operative and nonoperative sides. No loss of ROM was noted as a result of the reconstruction.
Phase III Trial of Long-Term Adjuvant Androgen Deprivation After Neoadjuvant Hormonal Cytoreduction and Radiotherapy in Locally Advanced Carcinoma of the Prostate: The Radiation Therapy Oncology Group Protocol 92–02
Authors: Gerald E. Hanks, Thomas F. Pajak, Arthur Porter, David Grignon, Harmart Brereton, Varagur Venkatesan, Eric M. Horwitz, Colleen Lawton, Seth A. Rosenthal, Howard M. Sandler, William U. Shipley
Journal: Journal of Clinical Oncology (2003)

Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL.Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study.The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear.The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.
The contents of consciousness: A neuropsychological conjecture
Authors: Jeffrey A. Gray
Journal: Behavioral and Brain Sciences (1995)

Abstract Drawing on previous models of anxiety, intermediate memory, the positive symptoms of schizophrenia, and goal-directed behaviour, a neuropsychological hypothesis is proposed for the generation of the contents of consciousness. It is suggested that these correspond to the outputs of a comparator that, on a moment-by-moment basis, compares the current state of the organism's perceptual world with a predicted state. An outline is given of the information-processing functions of the comparator system and of the neural systems which mediate them. The hypothesis appears to be able to account for a number of key features of the contents of consciousness. However, it is argued that neitherthis nor any existing comparable hypothesis is yet able to explain why the brain should generate conscious experience of any kind at all.
Efficacy and Safety of Omalizumab in Chronic Idiopathic/Spontaneous Urticaria (CIU/CSU): Results From a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Thomas Casale, Marcus Maurer, Hsin-Ju Hsieh, Janice Canvin, Sarbjit S. Saini, Clive Grattan, Ana Gimenez-Arnau, Allen P. Kaplan, Karin Rosen
Journal: Journal of Allergy and Clinical Immunology (2013)
775 HCV REPLICATION REGULATES GENES IMPLICATED IN MRNA TRANSLATION AT THE POST-TRANSCRIPTIONAL LEVEL
Authors: H. Colman, C. Seoul, C. Hernandez, S. Pierredon, A. Bihoudée, R. Houlgatte, S. Vagner, A. Rosenberg, C. Feray
Journal: Journal of Hepatology (2011)
Breast Cancer Chemoprevention Phase I Evaluation of Biomarker Modulation by Arzoxifene, a Third Generation Selective Estrogen Receptor Modulator
Authors: Carol J. Fabian, Bruce F. Kimler, Julie Anderson, Ossama W. Tawfik, Matthew S. Mayo, William E. Burak, Joyce A. O’Shaughnessy, Kathy S. Albain, David M. Hyams, G. Thomas Budd, Patricia A. Ganz, Edward R. Sauter, Samuel W. Beenken, William E. Grizzle, John P. Fruehauf, Dora W. Arneson, James W. Bacus, Michael D. Lagios, Karen A. Johnson, Doris Browne
Journal: Clinical Cancer Research (2004)

Arzoxifene, a new selective estrogen receptor modulator with strong breast antiestrogen activity and absence of uterine agonist activity, was explored as a potential chemoprevention agent. We performed a multi-institutional evaluation of arzoxifene in women with newly diagnosed ductal carcinoma in situ or T1/T2 invasive cancer.In a Phase IA trial, 50 pre- or postmenopausal women were randomized to 10, 20, or 50 mg of arzoxifene daily in the interval between biopsy and re-excision or were enrolled as no-treatment controls. In a Phase IB trial, 76 postmenopausal women were randomized to 20 mg of arzoxifene versus matched placebo. Serum specimens collected at entry and at re-excision were assayed for various hormones and growth factors. Tissue from biopsies (estrogen receptor + and/or progesterone receptor +) and re-excision specimens was evaluated immunohistochemically for proliferation (Ki-67 by MIB-1 and proliferating cell nuclear antigen) and other biomarkers.In both trials, increases in serum sex hormone binding globulin were noted, as were decreases in insulin-like growth factor (IGF)-I and the IGF-I:IGF binding protein-3 ratio (P < 0.007 versus control/placebo). For 45 evaluable women in Phase IA, decreases in proliferation indices were more prevalent for arzoxifene (particularly 20 mg) than for controls. For 58 evaluable women in Phase IB, a decrease in estrogen receptor expression for arzoxifene was observed compared with no change with placebo (P = 0.0068). However, decreases in proliferation indices for arzoxifene were not statistically different from placebo, perhaps due to a confounding effect of stopping hormone replacement therapy before entry.Given the favorable side effect profile and the biomarker modulations reported here, arzoxifene remains a reasonable candidate for additional study as a breast cancer chemoprevention agent.
Double-blind comparison of efficacy and gastroduodenal safety of diclofenac/misoprostol, piroxicam, and naproxen in the treatment of osteoarthritis.
Authors: J A Melo Gomes, S H Roth, J Zeeh, G A Bruyn, E M Woods, G S Geis
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To compare the efficacy and gastroduodenal safety of a fixed-dose combination of diclofenac sodium 50 mg and misoprostol 200 micrograms twice daily with those of piroxicam 10 mg twice daily and naproxen 375 mg twice daily in patients with osteoarthritis. METHODS--A 4 week, randomised, double-blind, parallel-group, multicentre study was conducted in 643 patients with symptomatic osteoarthritis of the hip and/or knee, who required continuous non-steroidal anti-inflammatory drug therapy for 4 weeks and who were without significant upper gastrointestinal damage as confirmed by endoscopy. RESULTS--For patients who had pre- and post-treatment endoscopic examinations, gastroduodenal ulcers developed in 3 (1.5%) of 200 patients treated with diclofenac/misoprostol, 21 (10.3%) of 204 piroxicam-treated patients, and 17 (8.6%) of 198 patients receiving naproxen (Chi square = 13.771, p = 0.001). The improvement in the osteoarthritis severity index was greater in the diclofenac/misoprostol group than in the piroxicam group (p = 0.004). Changes in physician and patient global assessments showed no significant differences between treatment groups. The incidences of diarrhoea and abdominal pain were higher in the diclofenac/misoprostol group than in the piroxicam and naproxen groups. CONCLUSIONS--Diclofenac/misoprostol at twice daily dosing is associated with significantly fewer gastroduodenal ulcers than either piroxicam or naproxen. The efficacy of diclofenac/misoprostol in treating the signs and symptoms of osteoarthritis is at least comparable to that of piroxicam and naproxen.
Nerve–Cancer Cell Cross-talk: A Novel Promoter of Tumor Progression
Authors: Phillip Jobling, Jay Pundavela, Sonia M.R. Oliveira, Séverine Roselli, Marjorie M. Walker, Hubert Hondermarck
Journal: Cancer Research (2015)

Recent studies have revealed the essential role played by nerves in tumor progression. Nerves have been shown to infiltrate the tumor microenvironment and actively stimulate cancer cell growth and dissemination. This mechanism involves the release of neurotransmitters, such as catecholamines and acetylcholine, directly into the vicinity of cancer and stromal cells to activate corresponding membrane receptors. Conversely, the secretion of neurotrophic growth factors by cancer cells drives the outgrowth of nerves in solid tumors. This reciprocal interaction between nerves and cancer cells provides new insights into the cellular and molecular bases of tumorigenesis and points to the potential utility of antineurogenic therapies. This review will discuss our evolving understanding of the cross-talk between nerves and cancer cells.
Endogenous Vascular Hydrogen Peroxide Regulates Arteriolar Tension In Vivo
Authors: Tatsiana Suvorava, Nadine Lauer, Stephanie Kumpf, Ralf Jacob, Wilfried Meyer, Georg Kojda
Journal: Circulation (2005)

Although many studies suggested direct vasomotor effects of hydrogen peroxide (H2O2) in vitro, little is known about the vasomotor effects of H2O2 in vivo.We have generated mice overexpressing human catalase driven by the Tie-2 promoter to specifically target this transgene to the vascular tissue. Vessels of these mice (cat++) expressed significantly higher levels of catalase mRNA, protein, and activity. The overexpression was selective for vascular tissue, as evidenced by immunohistochemistry in specimens of aorta, heart, lung, and kidney. Quantification of reactive oxygen species by fluorescence signals in cat++ versus catalase-negative (catn) mice showed a strong decrease in aortic endothelium and left ventricular myocardium but not in leukocytes. Awake male cat++ at 3 to 4 months of age had a significantly lower systolic blood pressure (sBP, 102.7+/-2.2 mm Hg, n=10) compared with their transgene-negative littermates (catn, 115.6+/-2.5 mm Hg, P=0.0211) and C57BL/6 mice (118.4+/-3.06 mm Hg, n=6). Treatment with the catalase inhibitor aminotriazole increased sBP of cat++ to 117.3+/-4.3 mm Hg (P=0.0345), while having no effect in catn (118.4+/-2.4 mm Hg, n=4, P>0.05). In contrast, treatment with the NO-synthase inhibitor nitro-L-arginine methyl ester (100 mg.kg BW(-1).d(-1)) increased sBP in cat++ and C57Bl/6 to a similar extent. Likewise, phosphorylation of vasodilator-stimulated phosphoprotein in skeletal muscle, left ventricular myocardium, and lung was identical in cat++ and catn. Endothelium- and NO-dependent aortic vasodilations were unchanged in cat++. Aortic KCl contractions were significantly lower in cat++ and exogenous H2O2 (10 micromol/L)-induced vasoconstriction.These data suggest that endogenous H2O2 may act as a vasoconstrictor in resistance vessels and contribute to the regulation of blood pressure.