tbuckley/cabot-search huggingface dataset:
Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis
Authors: Cécile Gaujoux-Viala, Jackie Nam, Sofia Ramiro, Robert Landewé, Maya H Buch, Josef S Smolen, Laure Gossec
Journal: Annals of the Rheumatic Diseases (2014)

Objectives To update a previous systematic review assessing the efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA). Methods Two systematic reviews of the literature using PubMed, Embase and the Cochrane library were performed from 2009 until January 2013 to assess the efficacy of csDMARDs (as monotherapy or combination therapy) in adults with RA, and the efficacy of glucocorticoids in early RA. A third systematic review was performed until March 2013 to assess the efficacy of tofacitinib by meta-analysis. Results For glucocorticoids, of 222 hits, five publications relating to four new trials were analysed for efficacy, confirming that initial treatment of RA with low-dose prednisone plus methotrexate (MTX) results in better clinical and structural outcomes at 1 and 2 years than treatment with MTX alone. For csDMARDs, of 498 studies, only two new studies were randomised controlled trials comparing MTX monotherapy with MTX in combination with another csDMARD without differences in glucocorticoid usage. Using tight control principles, clinical outcomes were no better with immediate triple therapy than with ‘step-up’ therapy. For tofacitinib, the pooled analysis of 10 trials showed that tofacitinib was more efficacious on signs and symptoms, disability and appeared to be more efficacious on structural damage than control treatment with placebo (OR (95% CI)—American College of Rheumatology 20% (ACR20) response: 2.44 (1.97 to 3.02)) or treatment with MTX (ACR20 response: 2.38 (1.66 to 3.43)). Conclusions Addition of low-dose glucocorticoids to csDMARD therapy produces benefits in early RA. Under tight control conditions, combination therapy with csDMARDs is no better than MTX monotherapy. Tofacitinib is a new DMARD with proven efficacy.
Accelerated tumor growth in mice deficient in DNAM-1 receptor
Authors: Akiko Iguchi-Manaka, Hirayasu Kai, Yumi Yamashita, Kai Shibata, Satoko Tahara-Hanaoka, Shin-ichiro Honda, Teruhito Yasui, Hitoshi Kikutani, Kazuko Shibuya, Akira Shibuya
Journal: The Journal of Experimental Medicine (2008)

Since the identification of ligands for human and mouse DNAM-1, emerging evidence has suggested that DNAM-1 plays an important role in the T cell– and natural killer (NK) cell–mediated recognition and lysis of tumor cells. However, it remains undetermined whether DNAM-1 is involved in tumor immune surveillance in vivo. We addressed this question by using DNAM-1–deficient mice. DNAM-1–deficient cytotoxic T lymphocyte (CTL) and NK cells showed significantly less cytotoxic activity against DNAM-1 ligand-expressing tumors in vitro than wild-type (WT) cells. The methylcholanthrene (MCA)-induced fibrosarcoma cell line Meth A expressed the DNAM-1 ligand CD155, and DNAM-1–deficient mice showed increased tumor development and mortality after transplantation of Meth A cells. Moreover, the DNAM-1–deficient mice developed significantly more DNAM-1 ligand-expressing fibrosarcoma and papilloma cells in response to the chemical carcinogens MCA and 7,12-dimethylbenz[a]anthracene (DMBA), respectively, than did WT mice. These results indicate that DNAM-1 plays an important role in immune surveillance of tumor development.
Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort
Authors: U Schotten
Journal: Cardiovascular Research (2002)

Objective: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. Methods: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca2+ and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force–frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca2+-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na+/Ca2+-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. Results: In 72 muscle preparations of SR patients contractile force was 10.9±1.8 mN/mm2 compared to 3.3±0.9 mN/mm2 (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force–frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na+/Ca2+-exchanger was upregulated by 67% in atria of AF patients. Conclusions: AF-induced atrial contractile dysfunction is not due to β-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca2+-channel and an increased Ca2+ extrusion via the Na+/Ca2+-exchanger seem to be responsible for the depressed contractility in remodeled atria.
Wegener's Granulomatosis, Systemic Vasculitis, and Antineutrophil Cytoplasmic Autoantibodies
Authors: R J Falk, J C Jennette
Journal: Annual Review of Medicine (1991)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Endoscopic versus histological characterisation of polyps during screening colonoscopy
Authors: Guido Schachschal, Michael Mayr, Andras Treszl, Klaus Balzer, Karl Wegscheider, Jens Aschenbeck, Alireza Aminalai, Rolf Drossel, Andreas Schröder, Mathias Scheel, Carl-Hermann Bothe, Jens-Peter Bruhn, Wolfgang Burmeister, Gabriela Stange, Christina Bähr, Ralf Kießlich, Thomas Rösch
Journal: Gut (2013)

<h3>Background</h3> As screening colonoscopy becomes more widespread, the costs for histopathological assessment of resected polyps are rising correspondingly. Reference centres have published highly accurate results for endoscopic polyp classification. Therefore, it has been proposed that, for smaller polyps, the differential diagnosis that guides follow-up recommendations could be based on endoscopy alone. <h3>Objective</h3> The aim was to prospectively assess whether the high accuracy for endoscopic polyp diagnosis as reported by reference centres can be reproduced in routine screening colonoscopy. <h3>Design</h3> Ten experienced private practice endoscopists had initial training in pit patterns. Then they assessed all polyps detected during 1069 screening colonoscopies. Patients (46% men; mean age 63 years) were randomly assigned to colonoscopy with conventional or latest generation HDTV instruments. The main outcome measure was diagnostic accuracy of in vivo polyp assessment (adenomatous vs hyperplastic). Secondary outcome measures were differences between endoscopes and reliability of image-based follow-up recommendations; a blinded post hoc analysis of polyp photographs was also performed. <h3>Results</h3> 675 polyps were assessed (461 adenomatous, 214 hyperplastic). Accuracy, sensitivity and specificity of in vivo diagnoses were 76.6%, 78.1% and 73.4%; size of adenomas and endoscope withdrawal time significantly influenced accuracy. Image-based recommendations for post-polypectomy surveillance were correct in only 69.5% of cases. Post hoc analysis of polyp photographs did not improve accuracy. <h3>Conclusions</h3> In everyday practice, endoscopic classification of polyp type is not accurate enough to abandon histopathological assessment and use of latest generation colonoscopes does not improve this. Image-based surveillance recommendations after polypectomy would consequently not meet guideline requirements. <h3>TrialRegNo</h3> NCT01297712.
Social aspects in assisted reproduction
Authors: S. Fasouliotis
Journal: Human Reproduction Update (1999)

In-vitro fertilization (IVF) and assisted reproductive techniques have become common practice in many countries today, regulated by established legislation, regulations or by committee-set ethical standards. The rapid evolution and progress of these techniques have revealed certain social issues that have to be addressed. The traditional heterosexual couple, nowadays, is not considered by many as the only 'IVF appropriate patient' since deviations from this pattern (single mother, lesbians) have also gained access to these treatments. Genetic material donation, age limitation, selective embryo reduction, preimplantation genetic diagnosis, surrogacy and cloning are interpreted differently in the various countries, as their definition and application are influenced by social factors, religion and law. Financial and emotional stresses are also often described in infertile couples. Information as deduced from the world literature regarding IVF regulation, as well as about the existing religious, cultural and social behaviours towards these new technologies, is presented in this article in relation to the social aspects of assisted reproduction.
A10.21 Toll-Like Receptor Triggering of Human Basophils May Synergise with IgE-Mediated Activation in ACPA+ RA
Authors: Jolien Suurmond, Jeroen N Stoop, Aleida M Bakker, Tom WJ Huizinga, René EM Toes, Annemie JM Schuerwegh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Antibodies against citrullinated proteins (ACPA) are highly specific for rheumatoid arthritis (RA). Recently, we described a cellular immune response against citrullinated antigens that was only present in ACPA+ RA patients. This response was mediated via crosslinking IgE-ACPA bound to basophils, and suggests a major role for FcεRI-positive cells in the pathogenesis of RA. However, other mechanisms could also contribute to basophil activation in RA, for example through endogenous TLR ligands present in synovium, which are thought to contribute to chronicity of RA. As only limited information is present on TLR-expression and function in human basophils, it is not known whether such mechanisms could activate basophils. Therefore we studied the activation of basophils via TLRs in combination with activation via IgE. Because recent studies in mice suggested that Th2-associated immune responses might be protective against arthritis, we also studied the effect of activated basophils on skewing of Th cells. <h3>Materials and Methods</h3> Basophils were isolated from healthy donors. Real-time quantitative PCR was used to evaluate RNA expression of TLRs. For TLR-mediated stimulation, basophils were stimulated with pathogen-associated TLR ligands, such as LPS. Activation of basophils was measured using flow cytometry and cytokine assays (multiplex assays and ELISA). Naïve T cells were stimulated in the presence of basophil supernatant to evaluate the effect of TLR- and IgE-mediated activation of basophils on T cell skewing. <h3>Results</h3> We show the presence of mRNA for TLR1-8 in human basophils, with transcripts of TLR-4 being most abundant. Basophils responded to TLR triggering with cytokine production, but not with degranulation. Remarkably, simultaneous triggering of basophils via TLR-ligands and IgE greatly enhanced cytokine production. Such synergy in cytokine production by basophils led to great enhancement of Th2 skewing. <h3>Conclusions</h3> Our data show that human basophils functionally express TLRs and that the activation via these receptors can synergise with IgE-mediated activation. These findings provide a new perspective on the role of basophils and IgE-ACPA in combination with endogenous TLR ligands as a contributor to Th2 responses in RA patients.
Infliximab for Maintenance of Glucocorticosteroid-Induced Remission of Giant Cell Arteritis
Authors: Gary S. Hoffman, Maria C. Cid, Karen E. Rendt-Zagar, Peter A. Merkel, Cornelia M. Weyand, John H. Stone, Carlo Salvarani, Weichun Xu, Sudha Visvanathan, Mahboob U. Rahman
Journal: Annals of Internal Medicine (2007)

Background: Tumor necrosis factor-α is present in arteries in giant cell arteritis. Objective: To evaluate the efficacy of infliximab, an anti–tumor necrosis factor-α agent, in giant cell arteritis. Design: Randomized, controlled trial. Setting: 22 sites in the United States, the United Kingdom, Belgium, Italy, and Spain. Patients: 44 patients with newly diagnosed giant cell arteritis that was in glucocorticosteroid-induced remission. Intervention: Participants were randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg of body weight) or placebo. Sixteen patients were assigned to glucocorticosteroid plus placebo, and 28 patients to glucocorticosteroid plus infliximab. Measurements: End points were measured through week 22, when an interim analysis resulted in early stopping of the planned 54-week trial. Primary end points were the number of patients who remained free of relapse through week 22 and adverse events. Secondary end points were time to first relapse, biomarkers, cumulative glucocorticosteroid dose, and the number of patients who remained relapse-free while the glucocorticosteroid dosage was tapered to 10 mg/d. Results: Infliximab therapy did not increase the proportion of patients without relapse at week 22 compared with placebo (43% vs. 50%, respectively; difference, −7 percentage points [95% CI, −38 to 23 percentage points; P = 0.65), nor did it increase the proportion of patients whose glucocorticosteroid dosages were tapered to 10 mg/d without relapse (61% vs. 75%, respectively; difference, −14 percentage points [CI, −42 to 14 percentage points]; P = 0.31). The incidence of infection was 71% with infliximab and 56% with placebo (difference, 15 percentage points [CI, −14 to 45 percentage points]). Limitations: The sample was too small to rule out modest effects of infliximab and included only patients with a new diagnosis. Only one dose of infliximab was evaluated, and the study was terminated early. Conclusions: This trial is too small to draw definitive conclusions, but it provides evidence that using infliximab as maintenance therapy in patients in glucocorticoid-induced remission of newly diagnosed giant cell arteritis is of no benefit and may be harmful. If infliximab has benefit, it is unlikely to be great. *For a list of the members of the Infliximab-GCA Study Group, see the Appendix. ClinicalTrials.gov registration number: NCT00076726.
A common clone of erythromycin-resistant Streptococcus pneumoniae in Greece and the UK
Authors: N. Fotopoulou, P.T. Tassios, D.V. Beste, S. Ioannidou, A. Efstratiou, E.R. Lawrence, J. Papaparaskevas, R.C. George, N.J. Legakis
Journal: Clinical Microbiology and Infection (2003)
A Novel Function of Junctional Adhesion Molecule-C in Mediating Melanoma Cell Metastasis
Authors: Harald F. Langer, Valeria V. Orlova, Changping Xie, Sunil Kaul, Darius Schneider, Anke S. Lonsdorf, Manuela Fahrleitner, Eun Young Choi, Vanessa Dutoit, Manuela Pellegrini, Sylvia Grossklaus, Peter P. Nawroth, Gustavo Baretton, Sentot Santoso, Sam T. Hwang, Bernd Arnold, Triantafyllos Chavakis
Journal: Cancer Research (2011)

Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified junctional adhesion molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C(-/-) mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis.
Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia
Authors: FS Muriel, E Svarch, S Pavlovsky, M Eppinger-Helft, J Braier, B Vergara, G Garay, R Kvicala, JM Divito, R Failace, E Dibar, E Jimenez
Journal: Blood (1983)
Knowledge of adult patients with cystic fibrosis about their illness.
Authors: S. P. Conway, M. N. Pond, A. Watson, T. Hamnett
Journal: Thorax (1996)

Adult patients need to understand their illness if the locus of control is to move from doctor to patient. Previous studies have shown important misconceptions and gaps in patients' knowledge about cystic fibrosis.Patients were invited to complete a multiple choice questionnaire covering all major aspects of cystic fibrosis. The questionnaire score was compared with a predicted score derived from the consultant, cystic fibrosis fellow, nurse, and physiotherapist ratings of patient knowledge. Data were obtained to provide a comprehensive patient profile and disease severity score. Both scores were tested for any associations with patient characteristics.Although patients had good general knowledge about the aspects of cystic fibrosis that impacted most on their daily lives--that is, respiratory and gastrointestinal problems--important gaps and misconceptions in these areas were still present. Knowledge and understanding of genetic and reproductive issues and the less common complications of cystic fibrosis were only moderate. Older more severely affected patients, and those who had more contact with the hospital caring team, had better multiple choice questionnaire knowledge scores. Professional carers were poor judges of the knowledge of individual patients.Important gaps persist into adult life in the knowledge patients with cystic fibrosis have about their illness. Objective assessment of these deficits is required so that each patient can be counselled according to his or her needs.
Signalling mechanisms underlying the metabolic and other effects of adipokines on the heart
Authors: M. Karmazyn, D. M. Purdham, V. Rajapurohitam, A. Zeidan
Journal: Cardiovascular Research (2008)

Adipokines represent a family of proteins released by adipocytes that affect various biological processes including metabolism, satiety, inflammation, and cardiovascular function. The first adipokine to be identified is leptin, a product of the obesity gene whose primary function is to act as a satiety factor. However, it is now recognized that leptin and many of the newly discovered adipokines produce effects on numerous organ systems including the heart. Indeed, various adipokines including leptin, adiponectin, and apelin exert potent and diverse cardiovascular effects which are mediated by their specific receptors and involve complex and multifaceted cell-signalling pathways. Among these are effects on the heart as well as blood pressure where leptin has been proposed to potentially contribute to obesity-related hypertension. In this review, we focus primarily on the diverse effects of adipokines on the heart and discuss the potential cell-signalling mechanisms underlying their actions. The potential role of adipokines in the regulation of cardiac metabolism and function is discussed. Discussion is also presented on the emerging role, both deleterious and salutary, of various adipokines in heart disease with an examination of the possible underlying mechanisms which contribute to these effects.
Alteration of Gastric Functions and Candidate Genes Associated With Weight Reduction in Response to Sibutramine
Authors: Maria I. Vazquez Roque, Michael Camilleri, Matthew M. Clark, Debra A. TePoel, Michael D. Jensen, Karen M. Graszer, Sarah A. Kalsy, Duane D. Burton, Kari L. Baxter, Alan R. Zinsmeister
Journal: Clinical Gastroenterology and Hepatology (2007)
Nickel Compounds Act through Phosphatidylinositol-3-kinase/Akt-Dependent, p70S6k-Independent Pathway to Induce Hypoxia Inducible Factor Transactivation and Cap43 Expression in Mouse Epidermal Cl41 Cells
Authors: Jingxia Li, Gerard Davidson, Yi Huang, Bing-Hua Jiang, Xianglin Shi, Max Costa, Chuanshu Huang
Journal: Cancer Research (2004)

Abstract Nickel compounds are a somewhat unique class of carcinogens. Previous studies have demonstrated that NiCl2 exposure leads to marked induction of hypoxia inducible factor 1 (HIF-1) in human osteosarcoma and BALB/c 3T3 cells, a transcription factor that has been considered to play an important role in tumor promotion and progression. However, the signal transduction pathways leading to HIF-1 induction are not well understood. The present study indicated that exposure of mouse epidermal Cl41 cells to either Ni3S2 or NiCl2 resulted in activation of phosphatidylinositol 3-kinase (PI-3K), Akt, and p70 S6 kinase (p70S6k). Inhibition of PI-3K, Akt, and p70S6k by overexpression of a dominant-negative mutant of PI-3K (Δp85) impaired nickel-induced HIF-1 transactivation. Furthermore, an overexpression of the dominant-negative Akt mutant (Akt-T308A/S473A) blocked nickel-induced Akt phosphorylation and HIF-1 transactivation, whereas inhibition of p70S6k activation by pretreatment of cells with rapamycin did not show significant inhibitory effects on HIF-1 transactivation induced by nickel compounds. Consistent with HIF-1 transactivation, inhibition of the PI-3K/Akt pathway by either overexpression of Δp85 or Akt-T308A/S473A caused dramatic inhibition of Cap43 protein expression induced by nickel compounds, whereas pretreatment of cells with rapamycin did not exhibit inhibition of Cap43 induction. These results demonstrated that nickel compounds induce HIF-1 transactivation and Cap43 protein expression through a PI-3K/Akt-dependent and p70S6k-independent pathway. This study should help us understand the signal transduction pathways involved in the carcinogenic effects of nickel compounds.
Successful Delivery of RRT in Ebola Virus Disease
Authors: Michael J. Connor, Colleen Kraft, Aneesh K. Mehta, Jay B. Varkey, G. Marshall Lyon, Ian Crozier, Ute Ströher, Bruce S. Ribner, Harold A. Franch
Journal: Journal of the American Society of Nephrology (2014)

AKI has been observed in cases of Ebola virus disease. We describe the protocol for the first known successful delivery of RRT with subsequent renal recovery in a patient with Ebola virus disease treated at Emory University Hospital, in Atlanta, Georgia. Providing RRT in Ebola virus disease is complex and requires meticulous attention to safety for the patient, healthcare workers, and the community. We specifically describe measures to decrease the risk of transmission of Ebola virus disease and report pilot data demonstrating no detectable Ebola virus genetic material in the spent RRT effluent waste. This article also proposes clinical practice guidelines for acute RRT in Ebola virus disease.