tbuckley/cabot-search huggingface dataset:
SP0070 Pain management in rheumatology – lessons from a pain in motion: From the joint to the brain, from analgesics to biologics
Authors: S. Perrot
Journal: Annals of the Rheumatic Diseases (2013)

Pain in rheumatology represents a frequent situation. For many years it has been considered as the prototypical nociceptive pain condition but recent findings may modify pathophysiological and treatment approaches. 1. Recent findings on pain mechanisms in rheumatic disorders: –in the periphery, bone has appeared as an important component of pain: imaging has demonstrated good correlations between bone abnormalities and pain intensity. –in the brain, arthritis pain induce changes and sensitization, with dysfunctional changes misdiagnosed as a neuropathic pain component. –arthritis pain is not a stable condition: exacerbations related to movement and at night could be related to different pathophysiological mechanisms. 2. Consequently, new therapeutic strategies have emerged, to be accepted by rheumatologists: –antidepressants may be effective in chronic joint pain, even without mood disorders. –NSAIDs have been limited in their use but the real place of old and recent opioids in this condition remains challenged. –the place of opioids has increased, even if efficacy of new opioids in rheumatological conditions is still controversial, while safety issues have been raised. 3. Biologic agents will be developed for joint pain: –New biological agents acting on NGF have demonstrated significant effect, but safety issues may limit their development. –Biologic agents developed in inflammatory rheumatisms like anti-TNF or anti-IL6 agents may exhibit peripheral but also central action. 4. Finally, adapted from RA treatment strategies, we may propose a new classification of analgesics: –Antinociceptive analgesics for acute flares, and changes related to motion or inflammation –-Pain Modifying Analgesics Agents (PMADs) for long term treatment, on chronic component. In conclusion, pain management remains a challenge in rheumatology. We aim to demonstrate that all rheumatologists should be aware of recent findings in pain, both in pathophysiology and treatment. This may lead to new concepts of pain management in rheumatological conditions, for the benefit of our patients. <h3>Disclosure of Interest</h3> S. Perrot Grant/Research support from: BMS, Consultant for: Grunenthal, Sanofi, Mundipharma, Pfizer, Lilly
Abstract 5100: Secretome proteomics to identify indicators for lung cancer treatment response prediction and monitoring
Authors: Tieneke B.M Schaaij-Visser, Natalie Proost, Remco Nagel, Sander R. Piersma, Thang V. Pham, Ruud H. Brakenhoff, Anton Berns, Connie R. Jimenez
Journal: Cancer Research (2011)

Abstract Lung cancer is currently the number one cause of cancer-related deaths worldwide. Five-year survival rates for both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are still less than twenty percent due to late stage of presentation, treatment failure and lack of biomarkers for personalized therapy. Aim of this study is to identify protein biomarkers that can be used for treatment response prediction and therapy monitoring. Rather than following a broad strategy by analyzing the proteome of whole cell or tissue lysates, we chose to use a more specific approach based on the assumption that the best tumor markers are shed or secreted by the tumor and can be detected in blood. Secretome (i.e. all proteins shed from or secreted by a cell or tissue) proteomics (Piersma SR et al. J Proteome Res. 2010 Apr 5;9(4):1913-22.) was performed on a set of tumors from conditional mouse models for SCLC and NSCLC (Meuwissen R et al. Oncogene. 2001 Oct 4;20(45):6551-8; Meuwissen R et al. Cancer Cell. 2003 Sep;4(3):181-9.), a set of human and mouse SCLC and NSCLC cell lines and a series of human NSCLC cell lines with a range of IC50-values for cisplatin (1.5 – 15 µM). Secretomes were obtained by collecting serum-free media from the cell lines or collecting PBS in which a tumor tissue piece had been incubated. In the secretome samples, up to 2,000 proteins can be identified with 80% reproducibility by label-free, shotgun nanoLC tandem mass spectrometry and quantified by spectral counting. The beta-binomial test (Pham TV et al. Bioinformatics. 2010 Feb 1;26(3):363-9.) is used to find significant differences in protein expression between the different secretomes and network analysis is performed to provide insight into the underlying cellular mechanisms. The secretomes from the mouse models are used to find proteins specifically secreted by either NSCLC or SCLC, while the comparison between the secretomes of the several human and mouse cell lines allows extrapolation of the results from the mouse models to the human situation. Furthermore, the analysis of the cell lines with various cisplatin IC50-values permits selection of the protein markers that are indicative of sensitivity or resistance. The results of the different proteomics analyses will be presented along with the most promising biomarker candidates and an overview of the functional network analysis. 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 5100. doi:10.1158/1538-7445.AM2011-5100
A Multistate, Foodborne Outbreak of Hepatitis A
Authors: Yvan J.F. Hutin, Vitali Pool, Elaine H. Cramer, Omana V. Nainan, Jo Weth, Ian T. Williams, Susan T. Goldstein, Kathleen F. Gensheimer, Beth P. Bell, Craig N. Shapiro, Miriam J. Alter, Harold S. Margolis
Journal: New England Journal of Medicine (1999)

We investigated a large, foodborne outbreak of hepatitis A that occurred in February and March 1997 in Michigan and then extended the investigation to determine whether it was related to sporadic cases reported in other states among persons who had consumed frozen strawberries, the food suspected of causing the outbreak.
Analyse morphologique et fonctionnelle quantitative de la muqueuse colique par endomicroscopie confocale
Authors: N Musquer, S Coquenlorge, A Bourreille, P Aubert, S Bruley des Varannes, JP Galmiche, G Lauwers, M Neunlist, E Coron
Journal: Endoscopy (2012)

L'endomicroscopie confocale par minisonde (ECM) permet une étude de la muqueuse digestive à un niveau cellulaire. La plupart des études a utilisé des critères subjectifs afin d'obtenir une analyse histologique endomicroscopique. Cependant, nous ne savons pas si l'ECM permet une analyse quantitative de la muqueuse. Les objectifs de cette étude étaient 1) d'identifier et de valider des critères quantitatifs pour l'évaluation de la muqueuse colique par ECM, et 2) de comparer un groupe de témoins à des patients atteints de maladie de Crohn (MC) en rémission clinique sur la base de ces critères.
Extensive Ga-67 Accumulation in Lymph Nodes and Cutaneous Metastases in Gastric Cancer
Authors: YOSHIHIRO NISHIYAMA, YUKA YAMAMOTO, KATASHI SATOH, HITOSHI TAKASHIMA, MOTOOMI OHKAWA, YUKIKO KAWASAKI, MASATADA TANABE
Journal: Clinical Nuclear Medicine (1997)

Ga-67 imaging showed multiple lymph nodes and cutaneous metastases in an 80-year-old man with poorly differentiated adenocarcinoma of the stomach. Ga-67 scintigraphy showed multiple focal areas of increased radioactivity in supraclavicular, mediastinal, abdominal, and inguinal lymph nodes. In addition, multiple foci of increased activity were noted throughout the extremities. Needle biopsy of the cutaneous mass in the left lower abdomen was found to be metastatic carcinoma. This case was unique, with ex-tensive and intensely increased Ga-67 activity in the lymph nodes and cutaneous masses.
The Diffusing Capacity as a Predictor of Arterial Oxygen Desaturation during Exercise in Patients with Chronic Obstructive Pulmonary Disease
Authors: Gregory R. Owens, Robert M. Rogers, Bernard E. Pennock, David Levin
Journal: New England Journal of Medicine (1984)

We evaluated 48 patients with chronic obstructive pulmonary disease by means of pulmonary-function and exercise testing to determine whether any tests of pulmonary function could predict the development of arterial desaturation during exercise. We found that only two indexes--diffusing capacity and forced expiratory volume in one second (FEV1)--were predictive of desaturation. The diffusing capacity was more specific and sensitive than FEV1. A diffusing capacity above 55 per cent of predicted was 100 per cent specific in excluding desaturation, as compared with an 82 per cent specificity for an FEV1 above 55 per cent of predicted. With this cutoff point, the sensitivity of the diffusing capacity was 68 per cent, as compared with 46 per cent for the FEV1. Both the frequency and the magnitude of arterial desaturation increased substantially when the diffusing capacity was below 55 per cent of predicted. Testing the diffusing capacity should be useful in identifying which patients with chronic obstructive lung disease are likely to become desaturated during exercise and may therefore benefit from oxygen therapy.
Abstract PL04-03: Cell signaling by receptor tyrosine kinases: From basic principles to cancer therapy
Authors: Joseph Schlessinger
Journal: Cancer Research (2012)

Abstract Receptor tyrosine kinases (RTKs) comprise a family of cell surface receptors that control many critical cellular processes. Various human diseases are caused by dysfunction in RTKs or in their intracellular signaling pathways. Stem Cell Factor (SCF) initiates its multiple cellular responses by binding to the extracellular region of the RTK KIT resulting in receptor dimerization and tyrosine kinase activation. We have determined the crystal structure of the entire extracellular region of KIT before and after SCF stimulation. The structures show that KIT dimerization is driven by SCF binding whose sole role is to bring two KIT molecules together. We have used X-ray crystallography, electron microscopy (EM) and biochemical experiments to determine the three dimensional structure of intact, SCF-stimulated KIT dimers. Several forms of dimeric KIT molecules with different asymmetric arrangements of the two tyrosine kinase domains were identified. These asymmetric contacts may represent specific interactions occurring between two KIT tyrosine kinase domains poised towards trans autophosphorylation. We propose that cooperative interactions mediated by multiple weak homotypic contacts between the extracellular, transmembrane and cytoplasmic regions of KIT are responsible for tyrosine kinase activation and cell signaling in normal and transformed cells. Sutent is a drug that blocks the tyrosine kinase activities of several RTKs including KIT and VEGFR2. Sutent has been approved by the FDA for the treatment of advanced kidney cancers, gastrointestinal tumors and for endocrine pancreatic cancers. A scaffold-based drug discovery approach was developed enabling the development of new families of inhibitors for protein kinases and other enzymes that play a role in cell signaling. V600E B-RAF mutant is an oncogenic mutation identified in approximately 50% of melanomas and in 4% of all solid tumors. By using a scaffold-based drug discovery approach, a potent inhibitor of V600E B-RAF mutant has been discovered designated PLX 4032 (Vemurafenib). Phase-I and-II clinical trials in multiple medical centers revealed 80% responses such as tumor shrinkage, delay in tumor progression and survival of melanoma patients harboring the B-RAF mutation. Primary endpoints of phase-III clinical trials in multiple medical centers were achieved to support Vemurafenib registration. 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 PL04-03. doi:1538-7445.AM2012-PL04-03
Asymptomatic Periostitis of the Navicular and Fifth Metatarsal Bones in a High Jumper
Authors: C Williams, B O'Brien, G Duffy
Journal: Clinical Nuclear Medicine (1998)

Exercise-induced periostitis of the tibia is well recognized. Cases involving the humerus also have been reported. A case of periostitis of the fifth metatarsal bone of the leading foot and in both right and left navicular bones in a high jumper is presented. This represents a further type of stress-induced periostitis in an athlete.
Reduction of Postprostatectomy Bleeding by Epsilon-Aminocaproic Acid
Authors: Edgardo Sack, Theodore H. Spaet, Ralph L. Gentile, Perry B. Hudson
Journal: New England Journal of Medicine (1962)

EPSILON-aminocaproic acid (EACA) is a potent inhibitor of plasminogen activation in relatively low concentrations (5 × 10–4M) and of plasmin at considerably higher concentrations (1 × 10–2M).1 , 2 This drug, first described by Japanese investigators, has the structural formula: Clinical studies have indicated that it is effective in hemorrhagic disorders associated with increased blood fibrinolytic activity,3 4 5 and its use in prostatic surgery was first suggested by McNicol and his associates.6 These investigators suggested that hemostasis in the prostatic bed might be disrupted by clot lysis induced by the presence in urine of urokinase, an activator of plasminogen. Administration of . . .
Melanin nanoparticles derived from a homology of medicine and food for sentinel lymph node mapping and photothermal in vivo cancer therapy
Authors: Maoquan Chu, Wangxi Hai, Zheyu Zhang, Fangjie Wo, Qiang Wu, Zefei Zhang, Yuxiang Shao, Ding Zhang, Lu Jin, Donglu Shi
Journal: Biomaterials (2016)
P178 INTERFERON ALPHA AND LAMBDA INHIBIT HBV REPLICATION WITH DISTINCT EFFICACY AND KINETICS OF GENE REGULATION IN HUMANIZED MICE
Authors: K. Giersch, L. Allweisss, T. Volz, A.W. Lohse, J. Petersen, M. Lutgehetmann, M. Dandri
Journal: Journal of Hepatology (2014)
Inefficacy of Immediate Node Dissection in Stage 1 Melanoma of the Limbs
Authors: U. Veronesi, J. Adamus, D. C. Bandiera, I. O. Brennhovd, E. Caceres, N. Cascinelli, F. Claudio, R. L. Ikonopisov, V. V. Javorskj, S. Kirov, A. Kulakowski, J. Lacour, F. Lejeune, Z. Mechl, A. Morabito, I. Rodé, S. Sergeev, E. van Slooten, K. Szczygiel, N. N. Trapeznikov, R. I. Wagner
Journal: New England Journal of Medicine (1977)

From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.
Scintigraphic Findings in Necrotizing Myopathy
Authors: CRISTINA NANNI, STEFANO FANTI, CARMINE PINTO, MOHSEN FARSAD, ANDREA MORETTI, ROBERTO FRANCHI, ANDREA MARTONI, NINO MONETTI
Journal: Clinical Nuclear Medicine (2003)

Necrotizing myopathy is a rare syndrome associated with several causes, including non–small-cell lung carcinoma. The authors present a case of this infrequently occurring disease, describe an unusual scintigraphic pattern, and show tracer uptake localized in soft tissues rather than the skeleton.
CARDIOLOGISTS REFER PATIENTS WITH AORTIC STENOSIS LATER AND WITH MORE SYMPTOMS THAN NON-CARDIOLOGISTS
Authors: Cassandra Ramm, John Vavalle, Tom Nguyen, Andrew Sampson, Pei-Hsiu Huang, Jill Foster, Vinod Thourani, Amar Krishnaswamy, Vladimir Demyanenko, Tracy Wang
Journal: Journal of the American College of Cardiology (2016)
Abstract 2357: Defining the Ezrin-CLIC4 interaction in osteosarcoma
Authors: Martin Mendoza, Ling Ren, Elai Davicioni, Daniel Wai, Timothy Triche, Chand Khanna
Journal: Cancer Research (2010)

Abstract Ezrin, a linker protein between the cytoskeleton and plasma membrane, plays an important role in the metastatic phenotype of cancers that includes osteosarcoma and rhabdomyosarcoma. To better understand the role of ezrin in metastasis, we have identified proteins that bind the N-terminus of ezrin using tandem mass spectrometry affinity chromatography. One of the mass spectrometry identified proteins is the p53, TNFα, and c-Myc regulated stress-response protein Chloride Intracellular Channel 4 (CLIC4). Under conditions of cell stress, CLIC4 has been shown to translocate to the nucleus and subsequently cause cell-cycle arrest and/or accelerate apoptosis in cancer cells including osteosarcoma. Emerging data from our lab suggests that ezrin may provide metastatic cells with an early survival advantage by helping to resist the stresses of metastasis and resultant apoptosis. Combining these two lines of reasoning, we hypothesized that ezrin prevents CLIC4 induced apoptosis during times of stress by maintaining CLIC4 out of the nucleus. Using cell free conditions we have demonstrated a direct relationship between ezrin and CLIC4 recombinant proteins and through co-immunoprecipitation in osteosarcoma cells. In addition, experiments to define the minimal binding determinants of the ezrin-CLIC4 interaction are currently underway. We have confirmed co-expression of ezrin and CLIC4 in multiple human osteosarcoma cell lines and human sarcomas using both immunohistochemistry and expression microarray. We have recently developed assays and reagents to monitor and manipulate CLIC4 nuclear localization under conditions of stress. The outcome of this work will be to define the nature and biological significance of the ezrin-CLIC4 interaction in metastasis. 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 2357.
Salicylism Accompanied by Respiratory Alkalosis and Toxic Encephalopathy
Authors: Henry W. Ryder, Murton Shaver, Eugene B. Ferris
Journal: New England Journal of Medicine (1945)

THE purpose of this article is to report a fatal case of salicylism. The case is of special interest for the following reasons: the drug was given in the usual doses, as determined by symptomatic effect; the course of intoxication was directly shown, by studies of the blood acid–base balance, to be a respiratory alkalosis; tetany and electrocardiographic changes were observed; and at autopsy diffuse toxic encephalopathy was found.The pH, whole-blood carbon dioxide content and hematocrit determinations were made as follows: Ten cubic centimeters of arterial blood was drawn into a dry syringe and immediately expelled into the cup . . .
Sequelae of Central-Nervous-System Enterovirus Infections
Authors: Clifford J. Sells, Robert L. Carpenter, C. George Ray
Journal: New England Journal of Medicine (1975)

The long-term effects of central-nervous-system enterovirus infections were examined in a controlled follow-up study of 19 children 2 1/2 to eight years of age who had been hospitalized with documented enterovirus infection 17 to 67 months before evaluation. Assessment included medical history, physical and neurologic examination, psychologic testing, and speech and hearing evaluation. Three children (16 per cent) had definite neurologic impairment, five (26 per cent) had possible impairment, and 11 (58 per cent) were free of detectable abnormalities. Children whose illness occurred during the first year of life, when compared to controls, were found to have significantly smaller mean head circumference (50.6 vs. 51.6 cm, P less than 0.033), significantly lower mean I.Q. (97 vs 115, P less than 0.007), and depressed languange and speech skills. Children whose illness occurred after the first year of life were not different from their controls. Children whith central-nervous-system enterovirus infection may have neurologic impairment when infection occurs in the first year of life.
P733Regulatory B cells from patients with coronary artery disease display numerical and functional alterations: a novel immune defect in atherosclerosis
Authors: I E Dumitriu, P Baruah, JC Kaski
Journal: Cardiovascular Research (2014)

Aim: T and B lymphocytes, the main cellular effectors of adaptive immunity, are deeply involved in the chronic inflammatory process that drives atherosclerosis. As the main source of antibodies, B cells were originally thought to be anti-atherogenic via production of neutralising antibodies against oxidised low density lipoprotein (LDL). Recent studies that depleted B lymphocytes in animal models of atherosclerosis have unravelled pro-atherogenic effects of conventional mature B2 B cells and protective roles for the innate B1a B-cell subset. Recently, B cells with regulatory function (Bregs) have also been identified in both animals and humans, but their role in atherosclerosis is currently unknown. Impairment of Bregs has been implicated in the pathogenesis of autoimmune disorders, but whether the same is true in atherosclerosis is yet to be determined. Our aim was to examine Bregs in patients with coronary atherosclerosis. Methods: Bregs were defined as CD19+CD24hiCD38hi B cells. The percentage and absolute number of Bregs was quantified in the circulation of patients with myocardial infarction (MI, n=60) and stable angina (SA, n=40), as well as in healthy subjects (n=30) using flow cytometry. The production of interleukin-10 (IL-10) by mature, memory and Breg cells was quantified by intracellular staining and flow cytometry. Results: We found a marked reduction in the percentage and absolute number of Bregs in patients with coronary atherosclerosis (MI and SA) compared to healthy subjects. No differences were noted in the percentage and absolute number of total B cells, mature and memory B cells in the study groups, suggesting a specific numerical deficit in Bregs in patients with coronary atherosclerosis. Furthermore, Bregs from patients with coronary atherosclerosis produced significantly less IL-10 in response to CpG and CD40L compared to Bregs from healthy subjects, while the production of IL-10 from mature and memory B cells was not impaired. We are now characterising the molecular mechanisms that underlie the defects in Bregs in patients with coronary atherosclerosis. Conclusion: Our data show for the first time that patients with coronary atherosclerosis harbour marked numerical and functional deficits in Breg cells that may tip the balance in favour of pro-inflammatory B and T lymphocytes. A better understanding of these defects may reveal novel targets for future therapies to quench the inflammatory process that drives atherosclerosis.
DETECTION OF LEFT ATRIAL AND LEFT ATRIAL APPENDAGE THROMBUS BY CARDIAC MAGNETIC RESONANCE IN PATIENTS UNDERGOING PULMONARY VEIN ISOLATION
Authors: Danai Kitkungvan, Faisal Nabi, Mohamed Ghosn, Amish Dave, Miguel Valderrabano, William Zoghbi, Dipan Shah
Journal: Journal of the American College of Cardiology (2015)