tbuckley/cabot-search huggingface dataset:
A5.16 TNF-α Response of Synovial Fluid Monocyte-Macrophages to ACPA Immune Complexes
Authors: Cyril Clavel, Florence Anquetil, Laurent Zabraniecki, Évelyne Verrouil, Guy Serre, Mireille Sebbag
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Autoantibodies to citrullinated proteins (ACPA) are specifically associated to rheumatoid arthritis (RA) and produced in the inflamed synovium where citrullinated fibrin, their main antigenic target, is abundant. Using a human in vitro model we showed that macrophages generated by differentiation of blood monocytes from healthy individuals or patients with RA secrete TNF-α in response to immune complexes formed by ACPA and citrullinated fibrinogen (ACPA-IC). Moreover while in both healthy individuals and RA patients the TNF-α response of macrophages was much higher than that of their monocyte precursors, the TNF-α production of blood monocytes and monocyte-derived macrophages from RA patients did not differ from that observed with the healthy controls. <h3>Objectives</h3> To further assess the impact of ACPA-IC on joint inflammation, we evaluated the TNF-α response they prompt in monocyte-macrophages isolated from the synovial fluid (SF) of patients with RA and with other arthritides. <h3>Materials and Methods</h3> SF samples were obtained from 7 patients with RA (4 ACPA-positive, 3 ACPA-negative) and 8 ACPA-negative control patients with various arthritides. Polymorphonuclear cells were eliminated by centrifugation over Ficoll or capture with CD15-conjugated magnetic beads then monocyte-macrophages further purified using CD14-beads (median purity: 95%). The purified cells were stimulated with IC generated by capture of ACPA from IgG fractions prepared from RA sera, on immobilised citrullinated fibrinogen, as described (Clavel, Arthritis Rheum, 2008). <h3>Results</h3> With SF monocyte-macrophages from both RA and control patients, secretion of TNF-α sometimes occurred in the absence of any stimulation. However in RA patients, irrespective of their ACPA status, TNF-α secretion increased when the cells were cultured on ACPA-IC (median (range) = 16 (2–110) pg/ml). Such activation was also observed with the SF monocyte-macrophages from control patients (184 (33–638) pg/ml). In the whole series of SF samples, the increase in TNF-α secretion was found to be highly significant (p &lt; 0.001). <h3>Conclusions</h3> In contrast with our previous observations on CD14-positive blood monocytes and on derived macrophages, it appears that CD14-positive monocyte-macrophages can be pre-activated in the SF and secrete TNF-α spontaneously, but that they can nevertheless be further activated by ACPA-IC. These properties are not restricted to RA patients and seem to be characteristic for the SF CD14-positive monocyte-macrophages. Since citrullinated fibrin and ACPA have been described in the SF of RA patients, it is highly probable that ACPA-IC play a direct pro-inflammatory role in the SF by inducing or enhancing TNF-α secretion by the SF monocyte-macrophages.
Metastatic Undifferentiated Spindle Cell Sarcoma of the Thyroid Gland Evaluated by 18F-FDG PET/CT
Authors: Giorgio Treglia, Massimo Bongiovanni, Gaetano Paone, Luca Ceriani, Luca Giovanella
Journal: Clinical Nuclear Medicine (2014)

We describe a rare case of metastatic undifferentiated spindle cell sarcoma (USCS) of the thyroid gland evaluated by 18F-FDG PET/CT. A 63-year-old male patient with histological diagnosis of USCS of the thyroid gland underwent 18F-FDG PET/CT for staging. PET/CT revealed increased radiopharmaceutical uptake corresponding to a thyroid mass and mild 18F-FDG uptake in a 7-mm lung nodule, which was diagnosed as USCS metastasis. Based on these findings, the patient was referred to surgery and chemotherapy, but he died 6 months later for disease progression.
Regional Ventilation and Perfusion after Lung Transplantation in Patients with Emphysema
Authors: Paul M. Stevens, Philip C. Johnson, Robert L. Bell, Arthur C. Beall, Daniel E. Jenkins
Journal: New England Journal of Medicine (1970)

Serial 133Xe ventilation and perfusion scans were done on two patients who underwent left-lung transplantation because of severe emphysema associated with alpha1 antitrypsin deficiency. In both, perfusion of the implants increased to nearly 70 per cent of total and was accompanied by a decrease in ventilation and volume to about 30 per cent of total. Under these circumstances the implants functioned largely as physiologic shunts. The remaining emphysematous lung increased in volume and received most of the ventilation but very little of the total perfusion. Patients with emphysema thus may be poor candidates for lung transplantation because the high vascular resistance and static compliance of the remaining emphysematous lung predispose it to further hypoperfusion and hyperinflation.
BM-17 * FINAL RESULTS OF A RANDOMIZED TRIAL TO IDENTIFY THE OPTIMAL PLANNING TARGET VOLUME IN IMAGE-GUIDED STEREOTACTIC RADIOSURGERY OF BRAIN METASTASES
Authors: J. Kirkpatrick, Z. Wang, J. Sampson, F. McSherry, J. Herndon, K. Allen, E. Duffy, Z. Chang, J. Hoang, C. Kelsey, D. Yoo, A. Cabrera, F.-F. Yin
Journal: Neuro-Oncology (2014)

BACKGROUND: Our objective was to identify an optimal margin for SRS of brain metastases, minimizing toxicity and local recurrence. METHODS: Adult patients with 1-3 brain metastases, no previous brain radiotherapy and KPS >70 were eligible for this IRB-approved trial. Individual lesions were randomized to 1 or 3mm uniform expansion of the gross tumor volume (GTV) defined on MRI. The resulting planning target volume (PTV) was treated to 24, 18 or 15Gy marginal dose for PTV diameters <2, 2-2.9 and 3-4.0cm, respectively, using a LINAC-based radiosurgery system with 3D image guidance. The primary endpoint was local recurrence (LR.) Secondary endpoints included neurocognition (mini-mental state exam, Trailmaking tests A/B), quality of life (QOL, FACT-Br), radionecrosis (RN), distant failure in the brain (DF) and overall survival (OS). RESULTS: Between February 2010 and November 2012, 49 patients with 80 brain metastases were treated. Median age was 61 years and median KPS 90, with the predominant histologies non-small-cell lung cancer (25 patients) and melanoma (8). 55, 19 and 6 lesions were treated with 24, 18 and 15Gy, respectively. PTV/GTV ratio, V12Gy and minimum dose to GTV were significantly higher in the 3mm group (all p < 0.01), while GTV was similar (p = 0.76.) At a median follow-up of 32.2 months, 11 patients are alive with median OS 10.6 months. One-year post SRS, DF was 45.7%. LR was observed in 3 of 69 lesions with sufficient follow-up imaging, (2 in the 1mm group, p = 0.51) with a one-year post-SRS LR rate of 6.7%. Biopsy-proven RN alone was observed in 6 lesions (5 in the 3mm group, p = 0.10). Three months post-SRS, no significant change in neurocognition or QOL was observed (p > 0.05 for all measures). CONCLUSION: SRS was well-tolerated with low rates of LR in both cohorts. Given the higher potential risk of RN, a 1mm margin appears more appropriate.
Retinopathy in Tropical Pancreatic Diabetes
Authors: Viswanathan Mohan, Rema Mohan, Ambady Ramachandran, Chamukuttan Snehalatha, Moopil Viswanathan
Journal: Diabetes Care (1987)

In a study of the retinopathy profile of 40 patients with tropical pancreatic diabetes, a form of secondary diabetes seen in tropical countries, diabetic retinopathy was detected in 13 patients. Ten patients had background retinopathy and three patients had proliferative retinopathy requiring laser photocoagulation. In two patients, fibrous retinitis proliferans was present. Three patients had evidence of diabetic maculopathy. To our knowledge, this is the first report of severe and sight-threatening retinopathy occurring with secondary diabetes. Retinopathy in these forms of diabetes has hitherto been considered to be rare or, if present, only of a mild background type.
Abstract 5017: DNA methylation array screening in salivary gland adenoid cystic carcinoma
Authors: Chunbo Shao, Marietta Tan, Justin A. Bishop, Ami R. Vikani, Patrick K. Ha
Journal: Cancer Research (2012)

Abstract Objective: DNA methylation alterations, with either gain or loss of CpG methylation in the promoter region, can alter the expression of tumor suppressor genes or oncogenes. This contributes to the tumorigenesis of human cancers, including salivary adenoid cystic carcinoma (ACC). In this study, we used a DNA methylation array (Illumina HumanMethylation27 BeadChip, San Diego, CA) to screen for novel oncogene and tumor suppressor gene (TSG) candidates under the control of promoter methylation in ACC. Methods: The Illumina HumanMethylation27 BeadChip Array was used to analyze the DNA methylation patterns of ∼14.000 genes at 27,578 CpG sites in 21 ACC and 13 normal salivary gland tissues. With our basic screening algorithm, we narrowed the list down to ∼100 tumor suppressor gene candidates (hypermethylated in tumor) and oncogene candidates (hypomethylated in tumor). Next, the differential methylation levels in the promoter region of candidates were validated by bisulfite genomic sequencing in four primary ACC and four normal salivary gland tissues. Candidate genes that showed differential methylation were then confirmed by analyzing gene re-expression in seven cell lines treated with 5-Aza deoxycytidine, a global demethylating agent. Furthermore, the expression levels of the candidate genes were examined by quantitative reverse transcription PCR (qRT-PCR) in a separate ACC cohort. Lastly, the DNA methylation levels of promising candidate genes were validated by quantitative methylation specific PCR (qMSP) in a larger ACC cohort. Results: With the methylation array, we initially identified 28 oncogene candidates which displayed relative hypomethylation and 64 TSG candidates that showed relative hypermethylation in ACC compared to normal tissues. After the above mentioned additional validation steps were performed, we settled on two promising candidates, PDE9A and TP53TG3, that were significantly hypomethylated and overexpressed in primary ACC tumors compared to normal salivary gland tissue. Furthermore, the expression of PDE9A and TP53TG3 demonstrated consistent upregulation after 5-aza-cytidine treatment of cancer cell lines, suggesting that promoter methylation does play in a role in controlling gene expression. Conclusions: The Illumina HumanMethylation27 BeadChip array is a reliable and efficient tool for analyzing global gene methylation. It is useful in screening for novel oncogene and TSG candidates controlled by promoter methylation in salivary gland ACC. PDE9A and TP53TG3 were identified as promising novel oncogene candidates in salivary gland ACC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5017. doi:1538-7445.AM2012-5017
551 A PROTEOMIC ROAD MAP OF THE HepaRG CELL LINE: METABOLIC PATHWAYS PRESENT AND THEIR RESPONSE TO ACETAMINOPHEN TREATMENT
Authors: G. Tascher, M. Plumel, V. Shevchenko, F. Noor, E. Heinzle, A. van Dorsselaer, F. Bertile
Journal: Journal of Hepatology (2013)
Drinking Water Contamination and the Incidence of Leukemia and Non-Hodgkin's Lymphoma.
Authors: P Cohn, J Klotz, F Bove, M Berkowitz, J Fagliano
Journal: Environmental Health Perspectives (1994)

>A study of drinking water contamination and leukemia and non-Hodgkin's lymphoma (NHL) incidence (1979-1987) was conducted in a 75-town study area. Comparing incidence in towns in the highest trichloroethylene (TCE) stratum (>5 microg/l) to towns without detectable TCE yielded an age-adjusted rate ratio (RR) for total leukemia among females of 1.43 (95% CI 1.07-1.90). For females under 20 years old, the RR for acute lymphocytic leukemia was 3.26 (95% CI 1.27-8.15). Elevated RRs were observed for chronic myelogenous leukemia among females and for chronic lymphocytic leukemia among males and females. NHL incidence among women was also associated with the highest TCE stratum (RR = 1.36; 95% CI 1.08-1.70). For diffuse large cell NHL and non-Burkitt's high-grade NHL among females, the RRs were 1.66 (95% CI 1.07-2.59) and 3.17 (95% CI 1.23-8.18), respectively, and 1.59 (95% CI 1.04-2.43) and 1.92 (95% CI 0.54-6.81), respectively, among males. Perchloroethylene (PCE) was associated with incidence of non-Burkitt's high-grade NHL among females, but collinearity with TCE made it difficult to assess relative influences. The results suggest a link between TCE/PCE and leukemia/ NHL incidence. However, the conclusions are limited by potential misclassification of exposure due to lack of individual information on long-term residence, water consumption, and inhalation of volatilized compounds.
SAT0034 Cardiac involvement in systemic sclerosis: The added value of magnetic resonance imaging
Authors: L. Gargani, A. Pingitore, D. De Marchi, S. Guiducci, M. Doveri, S. Bellando Randone, L. Bazzichi, C. Bruni, S. Bombardieri, M. Lombardi, E. Picano, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiac involvement in systemic sclerosis (SSc) affects the prognosis of the disease. Myocardial fibrosisis the pathological hallmark of this complication and has been reported in 50–80% of cases in necropsy. Echocardiography is the routine imaging tool to easily detect cardiac involvement, but it is not accurate to detect myocardial fibrosis. Delayed gadolinium enhancement (DE) cardiovascular magnetic resonance (CMR) is the gold-standard for myocardial fibrosis assessment <h3>Objectives</h3> To evaluate the added value of DE-CMR to echocolorDoppler in SSc patients. <h3>Methods</h3> After a thorough clinical characterization, 53 SSc patients (age =52±14, 95% females, 34% diffuse form) underwent, on the same day, a comprehensive echocardiogram, including tissue Doppler imaging (TDI), and a DE-CMR. <h3>Results</h3> Echocardiography showed normal systolic function (ejection fraction =64±6%) and wall motion score index (=1) in 53/53 (100%) patients, whereas DE-CMR showed a pattern of non-ischaemic myocardial fibrosis in 12/53 (23%) patients. In 2/53 patients (4%), T2-weighted CMR showed myocardial oedema, that resolved after steroid therapy. Among clinical (age, duration of disease, limited or cutaneous form, Rodnan skin score, activity score), echocardiographic (indexed left atrium and left ventricular volumes, right atrium and ventricular dimensions, 2-D and TDI parameters of left and right ventricular function and pulmonary arterial systolic pressure) and CMR parameters, only TDI mitral annulus E/E' was an independent predictor of the presence of myocardial fibrosis at multivariate analysis (hazard ratio 1.8; 95% confidence interval 1.1-3.1). <h3>Conclusions</h3> Subclinical cardiac involvement is relatively frequent in SSc. CMR can detect different patterns of reversible (by T2-weighted) and irreversible (by DE) cardiac involvement. Elevated E/E' at echocardiography may raise the suspicion of myocardial fibrosis. <h3>Disclosure of Interest</h3> None Declared
S143 Premature Ageing And Skeletal Muscle Dysfunction In Copd Patients: Development Of A Cell Culture Model
Authors: R. Lahkdar, G. Choudhury, J. McLeish, E. Drost, L. McGlynn, P. Shiels, W. MacNee, R. Rabinovich
Journal: Thorax (2014)

<h3>Introduction</h3> COPD is a disease of accelerated ageing, as increased cellular-ageing (senescence) occurs in the lungs of these patients. We aim at developing a primary skeletal muscle cell culture (Human skeletal muscle satellite cells [HSKMC]) model of muscle ageing to study the cascade of events that occur in muscle senescence <i>in vitro</i> and to explore the effect of inflammation (TNF alpha) and oxidative stress (H<sub>2</sub>O<sub>2</sub>), two of the putative mechanisms related to muscle dysfunction and/wasting, on muscle differentiation and on protein loss in differentiated cells. <h3>Methods and results</h3> HSKMC were cultured to senescence when the cells stopped replicating. DNA was isolated from cells in serial passages of culture. Telomere length, a marker of biological ageing, was measured by qPCR and expressed as the ratio of telomere repeat copy number to single gene copy number in the experimental sample relative to a control sample (relative T/S ratio) (n = 3). Preliminary results show a progressive shortening of telomere length with cellular ageing when comparing early (passage 2, 1.433 ± 0.05 relative T/S ratio) with a later passage (passage 15, 0.340 ± 0.2 relative T/S ratio) (Fig 1). <h3>Conclusion</h3> We have developed a novel <i>in vitro</i> model of ageing skeletal muscle cells, which will help us to assess the role of accelerated ageing in muscle dysfunction and/wasting in COPD patients. Dr Lakhdar was funded by an LTERS fellowship grant.
Rendezvous technique: double-balloon endoscopy and SpyGlass direct visualization system in a patient with severe stenosis of a choledochojejunal anastomosis
Authors: Masaaki Shimatani, Makoto Takaoka, Tsukasa Ikeura, Toshiyuki Mitsuyama, Kota Kato, Kazuichi Okazaki
Journal: Endoscopy (2014)

This is the first report on the successful rendezvous technique of double-balloon endoscopy (DBE) (EI-530B; Fujifilm, Osaka, Japan) combined with the percutaneous SpyGlass® direct visualization system (SDVS) (Boston Scientific Corp., Natick, MA, USA) to treat severe stenosis of a choledochojejunal anastomosis in a patient with pancreaticoduodenectomy.
Significance of Solitary Nontoxic Thyroid Nodules
Authors: John B. Vander, Eugene A. Gaston, Thomas R. Dawber
Journal: New England Journal of Medicine (1954)

IN 1948 an epidemiologic investigation of cardiovascular disease was begun in Framingham, Massachusetts. Careful palpation of the thyroid region was included in the cardiac evaluation of each patient. In view of the continued disagreement over the significance of solitary thyroid nodules as related to carcinoma it now seems timely to make a preliminary report of the number of single thyroid tumors found in this population to date, with the ultimate aim of determining, by periodic examination, their relation to the development of thyroid cancer. The purpose of this paper, therefore, is to report the number and prevalence of single, nontoxic . . .
Improving Drug-Therapy Decisions through Educational Outreach
Authors: Jerry Avorn, Stephen B. Soumerai
Journal: New England Journal of Medicine (1983)

Abstract Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain healthcare costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed "unadvertisements" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based "detailing" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures. (N Engl J Med 1983; 308:1457–63.)
Abstract 1801: Predictive diagnostics for the PI3 kinase inhibitor GDC-0941 in breast and ovarian cancer
Authors: Carol O'Brien, Jill Spoerke, Sankar Mohan, Ajay Pandita, Deepak Sampath, Jeffrey Wallin, Mark Lackner
Journal: Cancer Research (2010)

Abstract The class I phosphatidylinositol 3’ kinase (PI3K) plays a major role in proliferation and survival in a wide variety of human cancers. A key factor in successful development of drugs targeting the PI3K pathway is likely to be the identification of responsive patient populations with predictive diagnostic biomarkers. GDC-0941 is a pan-inhibitor of all 4 isoforms of class 1 PI3K that is currently undergoing testing in the clinic. The PI3 kinase pathway is generally regarded as the most frequently altered pathway in cancer, and an attractive hypothesis is that these alterations will help identify tumors where the pathway is particularly active and hence patients who are likely to receive benefit from treatment with a PI3 kinase inhibitor. We used a large panel of breast and ovarian cancer cell lines as well as in vivo xenograft models to evaluate candidate predictive biomarkers for GDC-0941. The approach involved pharmacogenomic profiling as well as analysis of gene expression datasets from tumor cells profiled at baseline or after GDC-0941 treatment. We found that models harboring key pathway alterations were generally sensitive to the anti-tumor effects of GDC-0941. We found that a number of models that do not harbor these alterations also showed sensitivity, suggesting alternative explanations for sensitivity and thus a need to identify additional diagnostic hypotheses. Gene expression studies identified a small number of genes whose expression appears to be intimately linked to pathway activation that may also be useful diagnostic markers. 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 1801.
Abstract 2744: SNP-SNP interaction between a microRNA and its target gene increases risk of non-melanoma skin cancer
Authors: Heather H. Nelson, Carmen J. Marsit, Jacquelyn K. Kuriger, Margaret R. Karagas
Journal: Cancer Research (2011)

Abstract Functional genetic variation in microRNA's has the potential to broadly impact disease processes given the large number of gene targets per microRNA. To date, there are only a few examples of functionally verified mirSNPs; among them is rs2910164 contained in the pre-mir-146a. mir-146a is an important modulator of immune responses, and therefore is of interest for non-melanoma skin cancer (NMSC), a highly antigenic cancer. Using a large population-based case control study of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in New Hampshire, we investigated the impact of this mirSNP on cancer risk, and potential interaction with one of its gene targets (RNASEL, rs486907). While there was no observed risk associated with the C allele of the mir-146a SNP (ORBCC = 0.91, 95% CI 0.74 – 1.10), ORSCC=1.06, 95% CI 0.86 – 1.30), there was a significant interaction between sunburn history and the mirSNP for BCC (pinteraction=0.002). In addition, there was strong interaction between the mir-146a SNP and genetic variation in its target gene RNASEL (BCC, pinteraction=0.01, SCC pinteraction=0.003). Importantly, our study is among the first to demonstrate snp-snp interaction in a microRNA and its target gene. Further, these data imply that RNASEL, an enzyme involved in cellular and viral RNA turnover, is controlled by this miRNA and that this process is important in skin cancer etiology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2744. doi:10.1158/1538-7445.AM2011-2744