tbuckley/cabot-search huggingface dataset:
AB0497 Simultaneous determination of anti-infliximab antibodies and residual infliximab levels to monitor anti-TNF therapy
Authors: S. Chollet-Martin, P. Nicaise-Roland, L. de Chaisemartin, S. Grootenboer-Mignot, G. Hayem, A.-L. Pelletier, A. Amiot, V. Descamps, Y. Bouhnik, O. Meyer
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Some patients with autoimmune inflammatory diseases and treated with infliximab (an anti-TNF therapy) are suspected of acquired therapeutic resistance and loss of response. Several therapeutic strategies are possible for those patients: increasing infliximab dosage or switching to another TNF-inhibitor or another therapy. However, most of the strategies are based on clinical data. <h3>Objectives</h3> The aim of this study was to evaluate the presence of anti-infliximab antibodies together with residual infliximab levels in such patients <h3>Methods</h3> We studied 36 patients presenting rheumatoid arthritis (n=20), psoriasis (n=2), Crohn disease (n=5), ulcerative colitis (n=4), spondylarthritis ankylosis (n=4) treated by infliximab and suspected of therapeutic loss response. For 20 of them, the samples were obtained just before the switch to another biotherapy. Infliximab levels and anti-infliximab antibodies were determined by ELISA (LISA-TRACKER, BMD, France) with a threshold of 10 ng/ml for anti-infliximab antibodies and 0.1 microg/ml for infliximab <h3>Results</h3> Anti-infliximab antibodies were detected in 21 patients (median: 131 ng/ml, range 10-200 ng/ml). Infliximab levels were weak in 25 patients (median: 0.16 microg/ml, range: &lt;0.1-0.41 microg/ml). In 20/25 patients (80%), the weak level of infliximab was associated to the presence of anti-infliximab antibodies. Interestingly, in sera of two patients obtained more than one year after the last infliximab perfusion, anti-infliximab antibodies were still present. Elevated infliximab levels were associated to the presence of anti-infliximab antibodies in only one patient. In 6 patients, the loss of infliximab response was not explained by the presence of anti-TNF antibodies or weak infliximab levels, suggesting that a switch to another biological agent could be more efficient than to another TNF inhibitor. <h3>Conclusions</h3> In conclusion, our preliminary results suggest that in patients suspected of loss of anti-TNF response, the weak residual level of infliximab was mostly related to the presence of anti-infliximab antibodies confirming the necessity in those patients to switch to another TNF-inhibitor instead of increasing infliximab doses. <h3>Disclosure of Interest</h3> None Declared
Vasodilator responses to moderate hypoxia after submaximal adenosine injection or coronary occlusion in isolated perfused guinea pig hearts.
Authors: D F Stowe
Journal: Circulation Research (1980)

My objective was to observe if coronary vasodilator responses after bolus (0.2 ml) intracoronary injection of adenosine (1-5000 /IM) or after coronary artery occlusion (5-30 seconds) are modified over a range from mild to severe hypoxia [outflow oxygen tension (PO2 V ) = 119 ± 9 to 10 ± 2 (mean ± SEM) torr].The vasculature of ten isolated, paced (240 beats/min), nonworking guinea pig hearts was perfused by the Langendorff technique with a fortified Krebs-Ringer solution at 37.5°C and at a constant pressure of 55 torr.Graded hypoxia was produced by randomly altering perfusate FO2 to one of five predetermined levels.Individually, maximal hypoxia, maximal adenosine injection, and 30second occlusion increased vascular conductance by 98, 100, and 98%, respectively.At constant myocardial oxygen consumption (MVO 2 ), PO2V was inversely proportional to baseline conductance (r = 0.42, P < 0.01); during normoxia (PO 2v = 119 torr) both log-dose adenosine concentration and occlusion period were directly proportional to peak conductance (r = 0.78, P < 0.01; r = 0.73, P < 0.01).Low doses of adenosine or short occlusions significantly shifted the conductance intercept to higher values but did not change individual PO2V vs. conductance slopes.Similar results were found in the relationship between PO 2v and overflow volume after adenosine injection or occlusion.Moreover, both the excess volume flow with low doses of adenosine and the volume of reactive hyperemia were unaffected by PO2V when MVO2 was unchanged.As hypoxia became more severe and MVO2 decreased, reactive hyperemia decreased and the flow debt increased.This study indicates that adenosine or coronary occlusion produces additive, noninteractive coronary vasodilation in the presence of tissue hypoxia.One possible explanation for these results is that as conductance rises, the common receptors for endogenous and exogenous adenosine become increasingly saturated.
Next‐Generation Sequencing Reveals Restriction and Clonotypic Expansion of Treg Cells in Juvenile Idiopathic Arthritis
Authors: Lauren A. Henderson, Stefano Volpi, Francesco Frugoni, Erin Janssen, Susan Kim, Robert P. Sundel, Fatma Dedeoglu, Mindy S. Lo, Melissa M. Hazen, Mary Beth Son, Ronald Mathieu, David Zurakowski, Neng Yu, Tatiana Lebedeva, Robert C. Fuhlbrigge, Jolan E. Walter, Yu Nee Lee, Peter A. Nigrovic, Luigi D. Notarangelo
Journal: Arthritis & Rheumatology (2016)

Objective Treg cell–mediated suppression of Teff cells is impaired in juvenile idiopathic arthritis (JIA); however, the basis for this dysfunction is incompletely understood. Animal models of autoimmunity and immunodeficiency demonstrate that a diverse Treg cell repertoire is essential to maintain Treg cell function. The present study was undertaken to investigate the Treg and Teff cell repertoires in JIA. Methods Treg cells (CD4+CD25+CD127 low ) and Teff cells (CD4+CD25−) were isolated from peripheral blood and synovial fluid obtained from JIA patients, healthy controls, and children with Lyme arthritis. Treg cell function was measured in suppressive assays. The T cell receptor β chain ( TRB ) was amplified by multiplex polymerase chain reaction and next‐generation sequencing was performed, with amplicons sequenced using an Illumina HiSeq platform. Data were analyzed using ImmunoSEQ, International ImMunoGeneTics system, and the Immunoglobulin Analysis Tools. Results Compared to findings in controls, the JIA peripheral blood Treg cell repertoire was restricted, and clonotypic expansions were found in both blood and synovial fluid Treg cells. Skewed usage and pairing of TRB variable and joining genes, including overuse of gene segments that have been associated with other autoimmune conditions, was observed. JIA patients shared a substantial portion of synovial fluid Treg cell clonotypes that were private to JIA and not identified in Lyme arthritis. Conclusion We identified restriction and clonotypic expansions in the JIA Treg cell repertoire with sharing of Treg cell clonotypes across patients. These findings suggest that abnormalities in the Treg cell repertoire, possibly engendered by shared antigenic triggers, may contribute to disease pathogenesis in JIA.
Abstract 5176: PPARγ acetylation governs differentiation function.
Authors: Lifeng Tian, Chenguang Wang, Fred K. Hagen, Mathew Casimiro, Anthony A. Sauve, Richard G. Pestell
Journal: Cancer Research (2013)

Abstract The peroxisome proliferator-activator receptor gamma (PPARγ) is a member of nuclear receptors (NRs) that plays an important role in the pathogenesis of human diseases, including obesity, type II diabetes and cancer. PPARγ regulates lipid homeostasis by activating the transcription of key genes that are responsible for lipid biosynthesis. NRs undergo post-translational modification including phosphorylation and acetylation. Direct nuclear receptor acetylation by histone acetyltransferases regulates ligand sensitivity and growth properties. Using mass spectrometry and in vivo labeling assays we showed that PPARγ is acetylated in cultured cells. Inhibition of endogenous TSA-sensitive and NAD-dependent deacetylase activity enhanced Pparγ acetylation. SIRT1 bound and deacetylated Pparγ at K154/155. These lysine residues of Pparγ were required for adipocyte differentiation function and determined distinct gene expression signaling pathways. The lysine residues governing sumoylation (K77) and acetylation (K154/155) were shown to have dissociable functions in regulating cell-cycle, gene expression, gene promoter activity, and protein stability. Breast tumor growth, de novo lipid synthesis, induction of autophagy and evasion of apoptosis was promoted by K154/155 and inhibited by K77 in vivo. Pparγ acetylation induced a gene signature that was increased in breast cancer, associated with a reduction in SIRT1 abundance and poor outcome. These studies suggest that the Pparγ lysine motif regulates both ligand-dependent receptor stability and receptor-dependent gene expression and cell functions. Pparγ and SIRT1 signaling converge in vivo to regulate breast tumor lipid metabolism and growth. Citation Format: Lifeng Tian, Chenguang Wang, Fred K. Hagen, Mathew Casimiro, Anthony A. Sauve, Richard G. Pestell. PPARγ acetylation governs differentiation function. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5176. doi:10.1158/1538-7445.AM2013-5176
THU0324 Inner Ear Dysfunction as an Expression of Atherosclerosis in Primary Antiphospholipid Syndrome
Authors: G. Medina, O. Vera-Lastra, M. P. Cruz-Domínguez, M. A. Saavedra-Salinas, L. J. Jara, J. Bonilla
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Microvascular oclussion may occur as part of the manifestations of the antiphospholipid syndrome (APS). One of these manifestations is Sensorineural hearing loss (SHL). <h3>Objectives</h3> To determine the prevalence of inner ear dysfunction in patients with primary APS and its association, if any, with carotid intima-media thickness (IMT). <h3>Methods</h3> From a cohort of 50 patients with primary APS we investigated the presence of inner ear dysfunction defined as SHL and/or labyrinthine affection based on the following symptoms: unilateral or bilateral sudden or progressive hearing loss, tinnitus and recurrent vertigo. Patients with the above-described symptoms underwent audiometric assessment. Those with vestibular symptoms also had balance function testing. Inner ear dysfunction was defined as hearing loss below normal values (mild hearing loss: audition loss &lt;35dB; moderate hearing loss: audition loss ranging from 35to 60dB; and severe hearing loss &gt;60 to 90dB) or presence of labyrinthine affection. Cardiovascular risk factors such as dyslipidemia, diabetes mellitus, arterial hypertension and carotid IMT were assessed. For the statistical analysis we employed descriptive statistics and chi square test. <h3>Results</h3> We detected 15 patients with hearing loss (30%) with a mean age of 51.6 years, mean APS disease evolution 12.7 years, treated with oral anticoagulants (INR between 2-3) and statins, 3 had arterial hypertension, 2, diabetes mellitus, 6 with dyslipidemia, and 8 had history of ischemic stroke. One patient presented sudden SHL that improved with corticosteroids, another one had left vestibular paresis as a stroke sequelae. Twelve patients were diagnosed with mild to moderate bilateral SHL and 3 with unilateral SHL. Only 2 patients had conductive hypoacusia due to otosclerosis, 5 had tinnitus and vertigo and were diagnosed as labyrinthine affection that improved with vestibular rehabilitation therapy. Three patients required hearing aid. Interestingly 12/15 patients (80%) with bilateral hearing loss presented carotid IMT with a mean of 1.2 mm ±0.2 (range from 0.8 to 2.9 mm). In contrast, 14/35 (40%) with carotid IMT did not have hearing loss (p&lt; 0.002). <h3>Conclusions</h3> Inner ear dysfunction is present in primary APS patients and is associated with carotid IMT. SHL may be an atherosclerosis expression. Other alternative therapies, besides the strict control of risk factors for atherosclerosis are needed. Auditive assessment must be performed at least once a year in order to identify and delay the presence of disability. <h3>References</h3> Mouadeb DA, et al. Antiphospholipid inner ear syndrome. Laryngoscope 2005;115: 879-83. Yehudai D, Shoenfeld Y, Toubi E. The autoimmune characteristics of progressive or sudden sensorineural hearing loss. Autoimmunity. 2006;39(2):153-8. <h3>Disclosure of Interest</h3> None Declared
Growth Stimulation of Microenvironment-Dependent Mouse Leukemias by Tumor-Promoting Phorbol Esters&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: H Hiai, Y Nishizuka
Journal: JNCI Journal of the National Cancer Institute (1981)

The effects of 12-O-tetradecanoylphorbol 13-acetate (TPA) and related tumor-promoting phorbol esters on 23 symbiotic cell lines from AKR thymic leukemias were studied. The phorbol derivatives with in vivo cocarcinogenic activity increased the viable yield of leukemia cells of most symbiotic cell lines in the absence of growth-supporting adherent cells. Particularly, in 10 cell lines remarkable growth stimulation was observed with 1 to 10 ng TPA/ml. The effect of TPA was reversible, since the leukemia cells exposed to TPA for 48 hours failed to grow without TPA or adherent cells. The leukemia cells from a symbiotic cell line could be maintained in TPA-containing medium for as long as 8 weeks without losing dependence. The leukemia cells were refractory to growth stimulation by TPA after they acquired the capability to grow independently. Furthermore, by affecting the leukemia cells, TPA and active tumor promoters inhibited pseudoemperipolesis (i.e., localization of leukemia cells under or between adherent cells), which is the basic cell interaction in symbiotic complexes. These effects of tumor-promoting phorbol esters are discussed with a special reference to the multistage hypothesis of leukemogenesis.
Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias
Authors: C Brendel, B Mohr, C Schimmelpfennig, J Müller, M Bornhäuser, M Schmidt, M Ritter, G Ehninger, A Neubauer
Journal: Leukemia (1999)
QUANTITATIVE DYNAMIC HIDA STUDIES FOR EVALUATION OF PEDIATRIC LIVER TRANSPLANT FUNCTION: METHODS AND RESULTS.
Authors: Theodore R. Hall, Randall A. Hawkins, Sanjiv S. Gambhir, Sung-cheng Huang, Hooshang Kangarloo, Michael E. Phelps, Ronald W. Busuttil
Journal: Clinical Nuclear Medicine (1988)

Hall, Theodore R.; Hawkins, Randall A.; Gambhir, Sanjiv S.; Huang, Sung-cheng; Kangarloo, Hooshang; Phelps, Michael E.; Busuttil, Ronald W. Author Information
Availability and Appropriateness of Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia in 10 Countries
Authors: George Silberman, Marcia G. Crosse, Eric A. Peterson, Richard C. Weston, Mary M. Horowitz, Frederick R. Appelbaum, Bruce D. Cheson
Journal: New England Journal of Medicine (1994)

Allogeneic bone marrow transplantation, a sophisticated and expensive procedure, is the only curative therapy for chronic myeloid leukemia (CML). We examined the availability and appropriateness of allogeneic bone marrow transplantation for CML in 10 economically advanced countries with diverse health care systems. For each country we obtained data on the likelihood of transplantation to treat CML in patients under the age of 55 years, the length of time from diagnosis to transplantation, and the stage of disease at the time of transplantation.
Abstract 3182: Decreased expression of PTEN enhances CXCR4-mediated proliferation and tumorigenesis in prostate cancer cells
Authors: Mahandranauth A. Chetram, Cimona V. Hinton
Journal: Cancer Research (2010)

Abstract The progression of human prostate cancer is a result of metastasis from the primary tumor to vital organs. Metastasis is a complex process that involves invasion, intravasation, extravasation, and metastatic colonization. To date, the biology underlying the various mechanisms of metastasis has not been fully elucidated. Chemokines are pro-inflammatory molecules that bind to chemokine receptors, which are members of the G-protein coupled receptor (GPCR) family. The interaction between chemokines and their receptors results in a diverse array of biological and biochemical functions, such as chemotaxis, hematopoiesis and angiogenesis. Likewise, neoplastic cells employ chemokines and their receptors to promote metastasis, and encourage cell survival. It has been observed that the CXCR4 chemokine receptor is overexpressed on the cell surface of prostate cancer cells, which directed metastatic cells to tissues where its CXCL12 ligand is overexpressed, such as the bones and lungs. The Phosphate and Tensin homolog deleted on chromosome 10 (PTEN) is the second most mutated tumor suppressor in human cancer, and has been shown to be mutated in metastatic prostate cancer cells. Gao et al demonstrated that reconstituted PTEN in lymphocytes down-regulated CXCR4-mediated chemotaxis towards its ligand, CXCL12. Additionally, progenitor PTEN-deficient smooth muscle cells (SMC) increased migration towards CXCL12-producing SMC, suggesting that an alteration in PTEN expression negatively regulated CXCR4-mediated events. We analyzed prostate cancer cells for the expression of CXCR4 by flow cytometry, and observed that CXCR4 was expressed in human metastatic prostate cancer cell lines, PC3 and LnCaP. We analyzed for the expression of PTEN, and observed no expression of PTEN in PC3 and LnCaP cells at the protein level by western blot, nor at the mRNA level in PC3 cells by PCR. Furthermore, when reconstituted with PTEN, PC3 cells demonstrated a mesenchymal to epithelial-like phenotypic change in morphology. Additionally, we observed that reconstituted PTEN inhibited CXCR4-meditated proliferation via an MTT assay. Therefore, we hypothesize that the absence of PTEN expression correlates with an up-regulation of CXCR4-mediated proliferation and tumorigenesis in prostate cancer cells. In summary, our results showed that PTEN induced an epithelial-like morphological change, and inhibited CXCR4-mediated proliferation in metastatic prostate cancer cell lines. In future studies, we will investigate if the reconstituted expression of functional PTEN regulates CXCR4-mediated metastatic events in prostate cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3182.
Démarche d'assurance qualité des ponctions sous échoendoscopie
Authors: P Robichaud, M Fabre, P Vielh, P Dartigues, F Abada, L Palazzo, P Burtin
Journal: Endoscopy (2012)

Il existe peu de données sur la démarche d'amélioration de la qualité en échoendoscopie (EE). Son application aux ponctions aurait un impact majeur sur la performance diagnostique.
The Suprapharmacologic Dosing of Antithrombin Concentrate for Staphylococcus Aureus-Induced Disseminated Intravascular Coagulation in Guinea Pigs: Substantial Reduction in Mortality and Morbidity
Authors: Craig M. Kessler, ZhaoCheng Tang, Helena M. Jacobs, Linda M. Szymanski
Journal: Blood (1997)
Effect of Parathyroidectomy on Bone Aluminum Accumulation in Chronic Renal Failure
Authors: Dennis L. Andress, Susan M. Ott, Norma A. Maloney, Donald J. Sherrard
Journal: New England Journal of Medicine (1985)

In some patients with chronic renal failure, bone mineralization becomes defective after parathyroidectomy for secondary hyperparathyroidism. Because aluminum deposition in bone is associated with impaired bone formation and osteomalacia, we retrospectively studied bone-biopsy specimens from patients on hemodialysis who were not exposed to dialysate contaminated with aluminum, to determine whether aluminum accumulation on bone surfaces was enhanced by parathyroidectomy. Serial biopsy specimens taken before and after parathyroidectomy revealed an increase in the rate of aluminum deposition on the surface of mineralized bone after parathyroidectomy in each of the six patients studied. The accelerated rate of aluminum accumulation could not be explained by changes in the oral aluminum intake. The mean rate of bone formation (+/- S.E.M.) before parathyroidectomy was higher in the six patients than in six control patients who did not undergo parathyroid surgery (586 +/- 147 vs. 237 +/- 85 micron2 per square millimeter per day; P less than 0.05). After parathyroidectomy, the rate of bone formation fell to levels below normal (148 +/- 32 vs. 311 +/- 29 micron2 per square millimeter per day; P less than 0.05) but was not significantly different from the rate in the control group (319 +/- 126 micron2 per square millimeter per day). We conclude that parathyroidectomy in patients with chronic renal failure is associated with enhanced aluminum deposition on the bone surface, possibly as a result of low bone formation. Patients with secondary hyperparathyroidism who may be candidates for parathyroidectomy should be evaluated for aluminum excess before surgery, so that treatment with aluminum chelation may be considered.
An outreaching model of tertiary difficult asthma care reduces adverse asthma outcomes and healthcare utilisation costs
Authors: Veeresh K. Patil, Christine Townshend, Frances Mitchell, Ramesh J. Kurukulaaratchy
Journal: European Respiratory Journal (2016)

Difficult asthma is a heterogeneous state, pragmatically defined by the British Thoracic Society (BTS) as "persistent symptoms and/or frequent exacerbations despite treatment at step 4 or step 5 treatment" [1, 2]. It is frequently associated with aggravating comorbidities, causes significant morbidity and healthcare costs, and requires rigorous systematic assessment and treatment approaches [3–7]. Though few exist, referral to a specialist centre with appropriate multidisciplinary expertise and supporting technical resource is recommended [8]. It is unclear whether such care can be effectively delivered in a peripheral healthcare setting. We report initial outcomes of such a care pathway on the Isle of Wight (IOW), UK. Outreaching specialist asthma care can significantly benefit patients with difficult asthma in peripheral settings <http://ow.ly/YClKM> We would like to thank all the staff at the David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.
P1135 ADDITION OF TELAPREVIR OR BOCEPREVIR TO PEG-RIB THERAPY INCREASES THE RISK OF INFECTIONS IN PATIENTS WITH HEPATITIS C-RELATED CIRRHOSIS (HCV-CH): A COMPARATIVE STUDY
Authors: M.-C. Londoño, C. Perelló, J. Cabezas, J.-A. Carrión, S. Lens, Z. Mariño, R. Rodríguez, S. Menéndez, J. Crespo, J.-L. Calleja, X. Forns
Journal: Journal of Hepatology (2014)