tbuckley/cabot-search huggingface dataset:
Successful treatment of adult-onset Still's disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade
Authors: J. Rech, M. Ronneberger, M. Englbrecht, S. Finzel, J. Katzenbeisser, K. Manger, B. Manger, G. Schett
Journal: Annals of the Rheumatic Diseases (2010)

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown aetiology.1 Based on the substantial acute phase responses observed in AOSD, we hypothesised that blockade of the interleukin 6R (IL-6R), neutralising the induction of the acute phase response by IL-6, could be a useful treatment in multidrug-resistant AOSD. We here report on three patients with AOSD who were refractory to standard treatment and cytokine blockade with anakinra and tumour necrosis factor (TNF) blockers and were subjected to treatment with tocilizumab. The characteristics of these three patients are summarised in table 1.

View this table:

Table 1 
Characteristics of patients



A 19-year-old woman was first diagnosed with AOSD in July 2006. Prednisone therapy was started, but multiple relapses occurred during the following 2 years requiring …
Long-Term Results of Catheter Ablation in Paroxysmal Atrial Fibrillation
Authors: Feifan Ouyang, Roland Tilz, Julian Chun, Boris Schmidt, Erik Wissner, Thomas Zerm, Kars Neven, Bulent Köktürk, Melanie Konstantinidou, Andreas Metzner, Alexander Fuernkranz, Karl-Heinz Kuck
Journal: Circulation (2010)

Paroxysmal atrial fibrillation (AF) naturally progresses toward chronic AF at an estimated rate of 15% to 30% over a 1- to 3-year period. Pulmonary vein (PV) isolation is increasingly performed for the treatment of drug-refractory paroxysmal AF. The long-term data on clinical outcome after circumferential PV isolation are limited.From 2003 to late 2004, 161 patients (121 men; age, 59.8±9.7 years) with symptomatic paroxysmal AF and normal left ventricular function underwent circumferential PV isolation guided by 3-dimensional mapping and double Lasso technique. Right-sided and left-sided continuous circular lesions encircling the ipsilateral PVs were placed with irrigated radiofrequency energy. The procedure end point was the absence of all PV spikes for at least 30 minutes after PV isolation verified by 2 Lasso catheters placed within the ipsilateral PVs. Sinus rhythm was present in 75 patients (46.6%) after the initial procedure during a median follow-up period of 4.8 years (0.33 to 5.5 years). A second procedure was performed in 66 and a third procedure in 12 patients. Recovered PV isolation conduction was observed in 62 of 66 patients (94.0%) during the second and in 8 of 12 patients (66.7%) during the third procedure. After a median of 1 (1 to 3) procedure, stable sinus rhythm was achieved in 128 of 161 patients (79.5%), whereas clinical improvement occurred in an additional 21 of 161 patients (13.0%) during a median follow-up of 4.6 years (0.33 to 5.5 years). Four patients in stable sinus rhythm died during follow-up. Progression toward chronic AF was observed in 4 patients (2.4%); however, only 2 patients reported symptoms.In patients with paroxysmal AF and normal left ventricular function, circumferential PV isolation results in stable sinus rhythm in the majority of patients, and low incidence of chronic AF was observed after ablation during up to 5 years of follow-up.
<i>FOXA1</i> Is a Potential Oncogene in Anaplastic Thyroid Carcinoma
Authors: Carmelo Nucera, Jerome Eeckhoute, Stephen Finn, Jason S. Carroll, Azra H. Ligon, Carmen Priolo, Guido Fadda, Mary Toner, Orla Sheils, Marco Attard, Alfredo Pontecorvi, Vânia Nose, Massimo Loda, Myles Brown
Journal: Clinical Cancer Research (2009)

FOXA1 is a mammalian endodermal transcription factor belonging to the human forkhead box gene family that plays a role in certain tumor types. Here, we investigated the potential role of FOXA1 in human thyroid carcinomas.We examined the level of FOXA1 expression and gene copy number by immunohistochemistry and fluorescence in situ hybridization, respectively, in a cohort of benign and malignant thyroid tumors. In addition, we examined the role of FOXA1 in the proliferation of an undifferentiated thyroid carcinoma cell line by short hairpin RNA-mediated silencing.We show that FOXA1 is overexpressed in human anaplastic thyroid carcinomas (ATC). In addition, we identify FOXA1 DNA copy number gain within the 14q21.1 locus in both an ATC cell line and human ATC cases. Silencing of FOXA1 in an ATC cell line causes G(1) growth arrest and reduction of cell proliferation. Moreover, we observe a potential link between FOXA1 and the cell cycle machinery by identifying p27(kip1) up-regulation on FOXA1 silencing.FOXA1 is overexpressed in aggressive thyroid cancers and involved in cell cycle progression in an ATC cell line. Therefore, FOXA1 may be an important oncogene in thyroid tumorigenesis and a potential new therapeutic target for the treatment of anaplastic thyroid cancers.
Inhaled sodium cromoglycate in children with asthma
Authors: A Edwards
Journal: Thorax (2002)

We note with interest the further correspondence concerning the systematic review of inhaled sodium cromoglycate as maintenance therapy in children with asthma1 from Professor M Silverman2 and Dr G Laszlo.3

Professor Silverman asked the authors to carry out separate calculations of the size of the treatment effect between inhaled sodium cromoglycate and placebo for school children and pre-school children. The results of these calculations show that the mean difference between inhaled sodium cromoglycate and placebo is greater for school children (cough 0.26, wheeze 0.29) than for pre-school children (cough …
SUSTAINED DELIVERY OF INSULIN-LIKE GROWTH FACTOR-1/HEPATOCYTE GROWTH FACTOR PROMOTES ENDOGENOUS CARDIAC REPAIR AND REGENERATION IN THE CHRONIC ISCHEMIC HEART
Authors: Stefan Koudstaal, Maartje Bastings, Georgina Ellison, Dries Feyen, Cheryl Waring, Daniele Torella, Bert Meijer, Joost Sluijter, Bernardo Nadal-Ginard, Pieter Doevendans, Patricia Dankers, Steven Chamuleau
Journal: Journal of the American College of Cardiology (2013)
Quantitative Ultrasonic Tissue Characterization Can Identify High-Risk Atherosclerotic Alteration in Human Carotid Arteries
Authors: Shin Takiuchi, Hiromi Rakugi, Katsuya Honda, Tohru Masuyama, Nobuaki Hirata, Hiroshi Ito, Ken Sugimoto, Yoshihiro Yanagitani, Koichi Moriguchi, Atsunori Okamura, Jitsuo Higaki, Toshio Ogihara
Journal: Circulation (2000)

Recently, ultrasonic tissue characterization of the composition of plaques has been performed in a quantitative fashion on the basis of integrated backscatter (IBS) analysis, but most of those studies have used high-frequency ultrasound to obtain microscopic images.We performed B-mode measurement and IBS signal analysis with acoustic densitometry with a 7.5-MHz linear-array transducer in freshly excised human aortas (n=58) (normal, atheromatous, and fibrous tissue) obtained at autopsy. Atheromatous and fibrous tissue had a similar intima-media thickness (IMT), but the IBS value in atheromatous specimens was lower than that in fibrous specimens. We further applied this method to human carotid ultrasonography. The subjects were young (80 regions), middle aged with 1 or no coronary risk factors (low risk) (120 regions), middle aged with >/=2 coronary risk factors (high risk) (240 regions), or elderly (80 regions) or were patients with myocardial infarction (MI) with multivessel disease (90 regions). The IMT was similar in middle-aged, elderly, and MI subjects. In contrast, the IBS value was significantly higher in elderly subjects and lower in high-risk middle-aged and MI subjects compared with that in low-risk middle-aged subjects. The percent of regions diagnosed as atheromatous (IBS less than mean minus 2-SD value of IBS in young subjects) was 11% in low-risk middle-aged subjects, 29% in high-risk middle-aged subjects, and 63% in the MI group.In conjunction with conventional B-mode imaging, IBS analysis with carotid ultrasonography appeared to provide prognostic information to identify a high-risk group with systemic atherosclerosis, which could lead to coronary heart disease in individuals with early-stage disease.
Results of the FFCD 9901 Trial in Early-Stage Esophageal Carcinoma: Is It Really About Neoadjuvant Therapy?
Authors: Brian G. Czito, Manisha Palta, Christopher G. Willett
Journal: Journal of Clinical Oncology (2014)

therapy does not improve survival and increases postoperative mortality in patients with early-stage disease. 13 However, patterns of failure analysis showed a significant improvement in local control in patients who were assigned to receive neoadjuvant therapy, nearly halving the rate of locoregional recurrence (29% v 15%). Disease recurrence rates were also significantly reduced in patients receiving neoadjuvanttreatment.TheselocalfailureratesmirrortheDutchtrial ratesoflocoregionalrecurrencereductionfrom34%(surgeryonly)to 14%(neoadjuvanttherapyandsurgery)inamoreadvancedgroupof patients.Thesedatahighlightthechallengeofsurgeryinextirpatingall locoregional disease even in patients with early-stage disease. How does one reconcile the differences in survival outcomes betweentheFrenchandDutchstudies?Thereareseveralpossibilities. First, small patient numbers in the FFCD 9901 trial reduce the statistical power of detecting a survival benefit, such as that seen in the Dutch study, despite similar reduction in disease recurrence rates in patients receiving neoadjuvant treatment. Next, the histologic subtypesweredifferentinthesetwostudies.Seventypercentofpatientsin the French study had a histologic diagnosis of squamous cell carcinoma compared with 23% in the Dutch study. Squamous cell carcinoma is a malignancy often arising in patients with longstanding histories of alcohol and tobacco use and associated comorbidities, whereas esophageal adenocarcinoma is associated with obesity, gastroesophageal reflux disease, and Barrett’s disease. The underlying biology and natural history of these two malignancies is different. Finally, the French study included more patients with early-stage disease(fewernode-positiveandT3patients)withcorrespondinghigh
From surgical to molecular scalpel: ERJ lung cancer series for 2009
Authors: C. Brambilla
Journal: European Respiratory Journal (2008)

Despite progress in tobacco control, at least in industrialised countries, lung cancer will remain the leading killer among cancers for the next decade. However, translation of molecular carcinogenesis discoveries to the clinical setting gives realistic hope of major improvements in early diagnosis and will, furthermore, enable therapy to be tailored thus reducing the mortality rate. Tobacco exposure accounts for 85–90% of lung cancer deaths 1. This range corresponds to 16,000–24,000 lung cancer deaths in the USA that are not attributable to tobacco carcinogens. Lung cancer in nonsmokers could, therefore, rank among the seven to nine most fatal cancers in the USA 2. An important study, of more than 630,000 people for incidence and 1.8 million people for mortality, has highlighted the major role of tobacco in lung cancer as its primary result and showed neither a temporal trend in favour of an increased incidence of lung cancer in nonsmokers nor a higher incidence in females, but supported claims that the death rate in males is higher than that in females; it also showed that further studies into the high incidence of lung cancer among females in Pacific Rim countries are necessary 2. If tobacco exposure remains the main cause, lung …
Molecular Evolution, Functional Variation, and Proposed Nomenclature of the Gene Family That Includes Sphingomyelinase D in Sicariid Spider Venoms
Authors: G. J. Binford, M. R. Bodner, M. H.J. Cordes, K. L. Baldwin, M. R. Rynerson, S. N. Burns, P. A. Zobel-Thropp
Journal: Molecular Biology and Evolution (2008)

The venom enzyme sphingomyelinase D (SMase D) in the spider family Sicariidae (brown or fiddleback spiders [Loxosceles] and six-eyed sand spiders [Sicarius]) causes dermonecrosis in mammals. SMase D is in a gene family with multiple venom-expressed members that vary in functional specificity. We analyze molecular evolution of this family and variation in SMase D activity among crude venoms using a data set that represents the phylogenetic breadth of Loxosceles and Sicarius. We isolated a total of 190 nonredundant nucleotide sequences encoding 168 nonredundant amino acid sequences of SMase D homologs from 21 species. Bayesian phylogenies support two major clades that we name α and β, within which we define seven and three subclades, respectively. Sequences in the α clade are exclusively from New World Loxosceles and Loxosceles rufescens and include published genes for which expression products have SMase D and dermonecrotic activity. The β clade includes paralogs from New World Loxosceles that have no, or reduced, SMase D and no dermonecrotic activity and also paralogs from Sicarius and African Loxosceles of unknown activity. Gene duplications are frequent, consistent with a birth-and-death model, and there is evidence of purifying selection with episodic positive directional selection. Despite having venom-expressed SMase D homologs, venoms from New World Sicarius have reduced, or no, detectable SMase D activity, and Loxosceles in the Southern African spinulosa group have low SMase D activity. Sequence conservation mapping shows >98% conservation of proposed catalytic residues of the active site and around a plug motif at the opposite end of the TIM barrel, but α and β clades differ in conservation of key residues surrounding the apparent substrate binding pocket. Based on these combined results, we propose an inclusive nomenclature for the gene family, renaming it SicTox, and discuss emerging patterns of functional diversification.
Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension
Authors: F. Perros, P. Dorfmüller, R. Souza, I. Durand-Gasselin, S. Mussot, M. Mazmanian, P. Hervé, D. Emilie, G. Simonneau, M. Humbert
Journal: European Respiratory Journal (2006)

In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean± sem number of DC-SIGN-positive cells·artery −1 of 100–300 μm diameter was 1.4±0.4 in controls versus 26.4±2.7 in IPAH. In rats, the number of OX-62-positive cells·artery −1 of 50–150 μm diameter was 0.5±0.2 in controls, and 0.7±0.5, 3.1±0.5 and 8.4±0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.
β-Particle–Emitting Radioactive Stent Implantation
Authors: A. J. Wardeh, I. P. Kay, M. Sabaté, V. L. M. A. Coen, A. L. Gijzel, J. M. R. Ligthart, A. den Boer, P. C. Levendag, W. J. van der Giessen, P. W. Serruys
Journal: Circulation (1999)

Background —This study represents the Heart Center Rotterdam’s contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, β-particle–emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation. Methods and Results —The radioisotope 32 P, a β-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 μCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n=12), the right coronary artery (n=8), or the left circumflex coronary artery (n=6). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13±4 mm, with a reference diameter of 2.93±0.47 mm. Minimum lumen diameter increased from 0.87±0.28 mm preprocedure to 2.84±0.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.85±0.69 mm, which resulted in a late loss of 0.99±0.59 mm and a late loss index of 0.53±0.35. No other major cardiac events occurred during the 6-month follow-up. Conclusions —The use of radioactive stents with an activity of 0.75 to 1.5 μCi is safe and feasible.
T-Cell Costimulation — Biology, Therapeutic Potential, and Challenges
Authors: Arlene H. Sharpe, Abul K. Abbas
Journal: New England Journal of Medicine (2006)

The immune system has the remarkable ability to defend against diverse microbial pathogens and yet not to respond to self. T cells are key mediators of the immune response, and their activation is tightly regulated to prevent autoreactivity. The processes of T-cell activation and self-tolerance are therefore potential targets for manipulation by drugs — hence, the recent phase 1 trial of a "superagonistic" monoclonal anti-CD28 antibody that was conducted in Britain on behalf of the German firm TeGenero, with the unexpected and devastating results described by Suntharalingam et al. in this issue of the Journal (pages 1018–1028).T-cell activation requires . . .
OX40 ligand plays an important role in the development of atherosclerosis through vasa vasorum neovascularization
Authors: M. Nakano, Y. Fukumoto, K. Satoh, Y. Ito, Y. Kagaya, N. Ishii, K. Sugamura, H. Shimokawa
Journal: Cardiovascular Research (2010)

AimsAtherosclerosis is characterized by infiltration of inflammatory cells and enhanced vasa vasorum formation, for which immunological mechanisms may be involved. OX40, a membrane-bound molecule of the tumour necrosis factor-receptor superfamily, is expressed by activated T-cells, while OX40 ligand (OX40L) is expressed in activated macrophages and endothelial cells. In this study, we thus examined whether the OX40/OX40L system is involved in the pathogenesis of atherosclerosis.
Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis
Authors: G Reynolds, J R Gibbon, A G Pratt, M J Wood, D Coady, G Raftery, A R Lorenzi, A Gray, A Filer, C D Buckley, M A Haniffa, J D Isaacs, C M U Hilkens
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objective</h3> A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. <h3>Methods</h3> Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). <h3>Results</h3> RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. <h3>Conclusions</h3> We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells.
Upper limb pyrophosphate tenosynovitis outside the carpal tunnel.
Authors: J.C Gerster, R Lagier
Journal: Annals of the Rheumatic Diseases (1989)

Three cases of calcium pyrophosphate dihydrate (CPPD) crystal deposits in tendon sheaths outside the carpal tunnel are reported. Crystals were shown by x ray diffraction analysis in one case and by compensated light microscopy in the other two. Surgical excision of the tendon synovial sheath had to be done in two cases (one case with CPPD crystal deposits).
Lung function disturbances and BAL IL-6 in adult patients with sickle cell disease in Bahrain
Authors: Adel Salah Bediwy, Nashwa Noor, Mohamed A. Hasanein
Journal: European Respiratory Journal (2011)

Sickle cell disease (SCD) is a common genetic disorder of hemoglobin in Bahrain with a lot of pulmonary complications either acute or chronic including its effect on pulmonary function tests (PFT). IL-6 is an inflammatory cytokine that was found to be high in serum of SCD patients.   Objective:  To study PFT and evaluate BAL IL-6 level in adult Bahraini patients with SCD and to correlate PFT values with BAL IL-6 and the recurrent occurrence of acute chest syndrome (ACS).   Methods:  Study was done on 120 subjects (2 groups): group 1 (20 healthy controls) and group 2 (100 adult Bahraini SCD patients during steady state). PFT were done to all subjects. BAL was done to 20 SCD patients and 5 control subjects to evaluate the BAL IL-6.   Results:  PFT was abnormal in 85% of SCD patients with restrictive pattern (60%), isolated low DLCO (17%), obstructive pattern (5%) and mixed obstructive and restrictive pattern (3%). BAL IL-6 was higher in SCD patients than in controls. In SCD patients, BAL IL-6 level had significant negative correlations with both FEV 1 , FVC, DLCO, and PaO 2 , with no significant correlation with TLC. There were significant positive correlations between BAL IL-6 and both age and number of ACS. There were significant negative correlations between ACS number and both FEV 1 , DLCO, and PaO 2  with no significant correlation between ACS number and both TLC and RV. There were significant negative correlations between age and both FEV 1 , TLC and DLCO.   Conclusion:  Abnormal PFT in adult Bahraini SCD patients was correlated to BAL IL-6 and number of ACS indicating that impaired lung functions in this category of patients is caused by repeated vascular occlusion and increased airway inflammation.