tbuckley/cabot-search huggingface dataset:
Mathematics and Oncology: A Match for Life?
Authors: Martine J. Piccart-Gebhart
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.12.068 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12668653 Mathematics and Oncology: A Match for Life? Martine J. Piccart-GebhartxMartine J. Piccart-GebhartSearch for articles by this author Show More Breast International Group, Jules Bordet Cancer Institute, Brussels, Belgium https://doi.org/10.1200/JCO.2003.12.068 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
The Multiplex Function of Nitric Oxide in (Auto)immunity
Authors: Christian Bogdan
Journal: The Journal of Experimental Medicine (1998)

Study of the role of nitric oxide (NO) in mammalian organisms has a history of complexities. When eukaryotic cells were demonstrated to generate NO from the aminoacid l-arginine, we were first stunned and then fascinated by the idea that a molecule with such a simple structure exerts messenger
Characterization of apolipoprotein A-I- and A-II-containing lipoproteins in a new case of high density lipoprotein deficiency resembling Tangier disease and their effects on intracellular cholesterol efflux.
Authors: M C Cheung, A J Mendez, A C Wolf, R H Knopp
Journal: Journal of Clinical Investigation (1993)

A 48-yr-old Caucasian female of central European origin (subject IM) with low plasma cholesterol and normal plasma triglyceride (TG) had extremely low apo A-I (6 mg/dl), A-II (5 mg/dl), and HDL cholesterol (2 mg/dl) levels. She had most of the clinical symptoms typically associated with Tangier disease, including early corneal opacities, yellow-streaked tonsils, hepatomegaly, and variable degrees of peripheral neuropathy, but had no splenomegaly. She had a myocardial infarction at age 46. Since HDL are postulated to be involved in the transport of excess cholesterol from peripheral tissues to the liver for degradation, and the ability of an HDL particle to promote cellular cholesterol efflux appears to be related to its density, size, and apo A-I and A-II contents, we isolated and characterized the HDL particles of this patient and all her first degree relatives (mother, a brother, and two children). The plasma A-I, A-II, and HDL cholesterol levels of all five relatives were either normal or high. Using anti-A-I and anti-A-II immunosorbents, we found three populations of particles in IM: one contained both apo A-I and A-II, Lp(AI w AII); one contained apo A-I but no A-II, Lp(AI w/o AII); and the third (an unusual one) contained apo A-II but no A-I, Lp(AII). Two-thirds of her plasma A-I and A-II existed in separate HDL particles, i.e., in Lp(AI w/o AII) and Lp(AII), respectively. Only Lp(AI w AII) and Lp(AI w/o AII) were present in the plasma of the relatives. All three populations of the patient's HDL particles had a normal core/surface lipid ratio, but the cores were enriched with TG. The apo A-I-containing particles, however, were considerably smaller and contained much less lipid than Lp(AII). Despite these unusual physicochemical characteristics, the apo A-I-containing particles and Lp(AII) were effective suppressors of intracellular cholesterol esterification in cholesterol-loaded human skin fibroblast. The patient's plasma apo D and lecithin cholesterol acyltransferase levels were reduced, with an increased proportion located in non-HDL plasma fractions. These findings are discussed in light of Tangier disease and other known HDL-deficiency cases, and the role of HDL in the maintenance of cell cholesterol homeostasis.
Anakinra for a refractory case of intermittent hydrarthrosis with a TRAPS-related gene mutation
Authors: Mariano Andrés, Eliseo Pascual
Journal: Annals of the Rheumatic Diseases (2012)

Intermittent hydrarthrosis (IH) is a rare condition characterised by its periodic schedule: recurrent self-remitting episodes of acute arthritis with a fixed periodicity; this clinical picture has been recognised as a clue for diagnosis for a long time.1 The pathogenesis of IH is unknown. An involvement of mastocytes has been reported.2 Interestingly, Canete et al 3 found mutations of the Mediterranean fever gene ( MEFV ) in a small series of patients with IH. For management of the disease, non-steroidal anti-inflammatory drugs, corticosteroids and colchicine are used, generally with good results, but some patients persist with recurrent episodes of arthritis. Here we report our experience with the interleukin-1 (IL-1) inhibitor anakinra in a patient with a …
Identification of the<i>PTPN22</i>functional variant R620W as susceptibility genetic factor for giant cell arteritis
Authors: A Serrano, A Márquez, S L Mackie, F D Carmona, R Solans, J A Miranda-Filloy, J Hernández-Rodríguez, M C Cid, S Castañeda, IC Morado, J Narváez, R Blanco, B Sopeña, M J García-Villanueva, J Monfort, N Ortego-Centeno, A Unzurrunzaga, B Marí-Alfonso, J Sánchez-Martín, E de Miguel, C Magro, E Raya, N Braun, J Latus, O Molberg, B A Lie, F Moosig, T Witte, A W Morgan, M A González-Gay, J Martín
Journal: Annals of the Rheumatic Diseases (2013)

To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA).
Urbanisation is associated with prevalence of childhood asthma in diverse, small rural communities in Ecuador
Authors: A. Rodriguez, M. Vaca, G. Oviedo, S. Erazo, M. E. Chico, C. Teles, M. L. Barreto, L. C. Rodrigues, P. J. Cooper
Journal: Thorax (2011)

<h3>Background</h3> Studies conducted in transitional communities from Africa and Asia have pointed to the process of urbanisation as being responsible for the increase in asthma prevalence in developing regions. In Latin America, there are few published data available on the potential impact of urbanisation on asthma prevalence. The aim of the present study was to explore how the process of urbanisation may explain differences in asthma prevalence in transitional communities in north-eastern Ecuador. <h3>Methodology/principal findings</h3> An ecological study was conducted in 59 communities in Esmeraldas Province, Ecuador. Indicators of urbanisation were grouped into three indices representing the processes associated with urbanisation: socioeconomic, lifestyle and urban infrastructure. Categorical principal components analysis was used to generate scores for each index and a fourth index—a summary urbanisation index—was derived from the most representative variables in each of the three indices. The authors analysed the associations between community asthma prevalence and the indices, as well as with each indicator variable of every group. The overall prevalence of asthma was 10.1% (range 0–31.4% between communities). Three of the four indices presented significant associations with community asthma prevalence: socioeconomic (r=0.295, p=0.023), lifestyle (r=0.342, p=0.008) and summary urbanisation index (r=0.355, p=0.006). Variables reflecting better socioeconomic status and a more urban lifestyle were associated with greater asthma prevalence. <h3>Conclusions</h3> These data provide evidence that the prevalence of asthma increases with increasing levels of urbanisation in transitional communities, and factors associated with greater socioeconomic level and changes towards a more urban lifestyle may be particularly important.
Severity of Escherichia coli bacteraemia is independent of the intrinsic virulence of the strains assessed in a mouse model
Authors: L. Landraud, F. Jauréguy, E. Frapy, G. Guigon, S. Gouriou, E. Carbonnelle, O. Clermont, E. Denamur, B. Picard, E. Lemichez, S. Brisse, X. Nassif
Journal: Clinical Microbiology and Infection (2011)
Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo.
Authors: P Paglia, C Chiodoni, M Rodolfo, M P Colombo
Journal: The Journal of Experimental Medicine (1996)

The priming of an immune response against a major histocompatibility complex class I-restricted antigen expressed by nonhematopoietic cells involves the transfer of that antigen to a host bone marrow-derived antigen presenting cell (APC) for presentation to CD8+ T lymphocytes. Dendritic cells (DC), as bone marrow-derived APC, are first candidates for presentation of tumor-associated antigens (TAA). The aim of this study was to see whether DC are able to prime in vivo antigen-specific cytotoxic T lymphocytes after exposure to a soluble protein antigen in vitro. Lacking a well-defined murine TAA, we took advantage of beta-galactosidase (beta-gal)-transduced tumor cell lines as a model in which beta-gal operationally functions as TAA. For in vivo priming both a DC line, transduced or not transduced with the gene coding for murine GM-CSF, and fresh bone marrow-derived DC (bm-DC), loaded in vitro with soluble beta-gal, were used. Priming with either granulocyte macrophage colony-stimulating factor-transduced DC line or fresh bm-DC but not with untransduced DC line generated CTL able to lyse beta-gal-transfected target cells. Furthermore, GM-CSF was necessary for the DC line to efficiently present soluble beta-gal as an H-2Ld-restricted peptide to a beta-gal-specific CTL clone. Data also show that a long-lasting immunity against tumor challenge can be induced using beta-gal-pulsed bm-DC as vaccine. These results indicate that effector cells can be recruited and activated in vivo by antigen-pulsed DC, providing an efficient immune reaction against tumors.
Local, systemic, and distant cytokine induction by selective nasal versus bronchial allergen provocation in a mouse model of airway allergy
Authors: G. Hens, P. Hellings, I. Meyts, B. Verbinnen, E. Dilissen, M. Adé, D. Bullens, J. Ceuppens
Journal: Journal of Allergy and Clinical Immunology (2005)
INDUCTION OF METASTASIS OF FROG CARCINOMA BY INCREASE OF ENVIRONMENTAL TEMPERATURE
Authors: Balduin Lucké, Hans Schlumberger
Journal: The Journal of Experimental Medicine (1949)

Metastasis of the kidney carcinoma of leopard frogs (Rana pipiens) has been induced by exposing tumor-bearing animals for approximately 50 days to a constant temperature of 28°C. Under these conditions 54 per cent of the frogs developed secondary growths, whereas in groups kept at 18° or at 7° metastatic dissemination was found in only 6 per cent. Moreover, at the elevated temperature the metastases were usually more numerous and more widely disseminated; they were also fairly uniform in size, suggesting that they had developed at nearly the same time. Dissemination of the kidney tumors was influenced by the nutritional state of the frogs, occurring more readily in well nourished than in poorly nourished animals. Periodic Roentgen ray examinations showed that the size of the primary tumors was not significantly or uniformly affected during the course of the experiments. No correlation was found between change in size of the kidney tumors and the incidence of their metastasis. Although the mechanism by which temperature induces metastasis of frog carcinoma cannot as yet be elucidated, previous experiments with this tumor indicate that certain factors at least may be involved: Elevation of temperature has been found to cause more ready detachment of cells of frog carcinoma in tissue culture; to bring about increased velocity of locomotion of the detached cells; to lead more promptly and efficiently to vascularization of transplants; and to effect their greater invasiveness.
Pulmonary Arterial Tree following Prolonged Experimental Reduction of Pulmonary Blood Flow
Authors: RICHARD L. NAEYE, BERT K. KUSSEROW, JULIUS H. JACOBSON
Journal: Circulation Research (1963)

A Blalock anastomosis between the left subclavian artery and the left pulmonary artery was performed on six dogs soon after birth. As an unexpected complication of surgery, blood flow through the left lungs of two of the dogs was greatly reduced. Over a period of 22 months, widespread arterial thromboses developed in these two lungs. The thrombotic lesions were comparable to those which develop in human beings with severe pulmonic valvular stenosis or atresia. Hypoxemia and polycythemia have often been implicated in the development of these lesions. Our study demonstrates that such lesions can be induced in the dog by reduction in pulmonary blood flow alone since hypoxemia and polycythemia were absent in our experimental animals.
A Gene Signature Predictive for Outcome in Advanced Ovarian Cancer Identifies a Survival Factor: Microfibril-Associated Glycoprotein 2
Authors: Samuel C. Mok, Tomas Bonome, Vinod Vathipadiekal, Aaron Bell, Michael E. Johnson, kwong-kwok Wong, Dong-Choon Park, Ke Hao, Daniel K.P. Yip, Howard Donninger, Laurent Ozbun, Goli Samimi, John Brady, Mike Randonovich, Cindy A. Pise-Masison, J. Carl Barrett, Wing H. Wong, William R. Welch, Ross S. Berkowitz, Michael J. Birrer
Journal: Cancer Cell (2009)
Intracellular Ca2+ waves, afterdepolarizations, and triggered arrhythmias
Authors: Yohannes Shiferaw, Gary L. Aistrup, J. Andrew Wasserstrom
Journal: Cardiovascular Research (2012)

Clinical studies have shown that sudden death is initiated by an ill-timed propagated ectopic beat that leads to fibrillation.1–4 However, the mechanism underlying these focal excitations is not completely understood. Experimental studies have demonstrated that abnormal calcium (Ca2+) cycling is a critical factor in the development of focal excitations.5–9 These excitations can be caused by spontaneous Ca2+ release (SCR) in the form of intracellular Ca2+ waves. These waves are initiated when Ca2+ release from a few Ca2+ release units (CRUs) on the sarcoplasmic reticulum (SR) causes regenerative release in adjoining units via Ca2+-induced Ca2+ release (CICR), causing Ca2+ wave propagation. The resulting depolarizing inward current through the electrogenic Na+–Ca2+ exchanger (NCX) depolarizes the cell membrane to threshold, producing a triggered beat.10–14

The relationship between subcellular Ca2+ waves and focal excitations in cardiac tissue is, however, still not completely understood. The basic unanswered question is how Ca2+ release within a population of cardiac cells can induce sufficient inward current to overcome the electrotonic load of the neighbouring cells. In this paper, we will discuss some key ideas that are essential in answering this question, focusing on the probabilistic nature of SCR and the importance of measuring the timing distribution of Ca2+ waves in multicellular populations in tissue. We will also discuss our recent results showing that the likelihood of a triggered beat is determined by the variance of the timing distribution, which is dictated by the time course of SR reloading.15,16 In addition, we will discuss our observations of a form of Ca2+ wave that is distinct from SCR. These Ca2+ waves occur only during rapid pacing and occur with a latency …
Cardiomyocyte-Specific Overexpression of Nitric Oxide Synthase 3 Prevents Myocardial Dysfunction in Murine Models of Septic Shock
Authors: Fumito Ichinose, Emmanuel S. Buys, Tomas G. Neilan, Elissa M. Furutani, John G. Morgan, Davinder S. Jassal, Amanda R. Graveline, Robert J. Searles, Chee C. Lim, Masao Kaneki, Michael H. Picard, Marielle Scherrer-Crosbie, Stefan Janssens, Ronglih Liao, Kenneth D. Bloch
Journal: Circulation Research (2006)

Myocardial dysfunction contributes to the high mortality of patients with endotoxemia. Although nitric oxide (NO) has been implicated in the pathogenesis of septic cardiovascular dysfunction, the role of myocardial NO synthase 3 (NOS3) remains incompletely defined. Here we show that mice with cardiomyocyte-specific NOS3 overexpression (NOS3TG) are protected from myocardial dysfunction and death associated with endotoxemia. Endotoxin induced more marked impairment of Ca 2+ transients and cellular contraction in wild-type than in NOS3TG cardiomyocytes, in part, because of greater total sarcoplasmic reticulum Ca 2+ load and myofilament sensitivity to Ca 2+ in the latter during endotoxemia. Endotoxin increased reactive oxygen species production in wild-type but not NOS3TG hearts, in part, because of increased xanthine oxidase activity. Inhibition of NOS by N G -nitro- l -arginine-methyl ester restored the ability of endotoxin to increase reactive oxygen species production and xanthine oxidase activity in NOS3TG hearts to the levels measured in endotoxin-challenged wild-type hearts. Allopurinol, a xanthine oxidase inhibitor, attenuated endotoxin-induced reactive oxygen species accumulation and myocardial dysfunction in wild-type mice. The protective effects of cardiomyocyte NOS3 on myocardial function and survival were further confirmed in a murine model of polymicrobial sepsis. These results suggest that increased myocardial NO levels attenuate endotoxin-induced reactive oxygen species production and increase total sarcoplasmic reticulum Ca 2+ load and myofilament sensitivity to Ca 2+ , thereby reducing myocardial dysfunction and mortality in murine models of septic shock.
Biopsy surveillance is still necessary in patients with Barrett's oesophagus despite new endoscopic imaging techniques
Authors: K Egger
Journal: Gut (2002)

<b>Background and aims:</b> Endoscopic surveillance including stepwise four quadrant biopsies (4QB) is still regarded as the standard approach in patients with Barrett's oesophagus (BO). Several methods such as dye staining with methylene blue (MB) and tissue autofluorescence (AF) have been advocated to reduce the number of biopsies. We assessed their sensitivity and specificity compared with the standard approach—that is, endoscopy with 4QB—in the surveillance of a mixed BO population. <b>Patients and methods:</b> Thirty five consecutive BO patients (mean age 64.9 years; 30 men, five women) were included in the study. AF endoscopy was followed by high resolution video endoscopy (VE) plus tissue staining with 0.5% MB. Biopsies were taken from any suspicious area found on any of the above tests, in addition to 4QB every 2 cm. The results were classified as either positive or negative for the various tests used. Histopathological results were used as the reference standard. <b>Results:</b> In the 35 study patients, a total of 345 biopsies showed low grade dysplasia (LGD) in 88 biopsies, high grade dysplasia (HGD) in 19 biopsies, and carcinoma in 12 biopsies. The sensitivity and specificity rates for AF and MB for the diagnosis of cancer or dysplasia versus BO mucosa without dysplasia were 21%/91% and 37%/91%, respectively. 4QB revealed five cancer/HGD areas and 76 LGD areas not detected by AF, MB, or VE. The additional yield of MB and AF over VE with 4QB concerned only one HGD area (in the vicinity of a cancer) and seven LGD areas. <b>Conclusions:</b> Due to their low sensitivity, AF and MB are not suitable techniques for reducing the high numbers of routine biopsies needed for finding additional foci of HGD or cancer. Careful endoscopic observation and stepwise four quadrant biopsy therefore still represent the gold standard for surveillance of Barrett's oesophagus.
Down-regulation of c-FLIP Enhances Death of Cancer Cells by Smac Mimetic Compound
Authors: Herman H. Cheung, Douglas J. Mahoney, Eric C. LaCasse, Robert G. Korneluk
Journal: Cancer Research (2009)

Abstract Smac mimetic compounds (SMC) are novel small molecules being developed for cancer therapy. The mechanism of SMC-induced sensitivity in cancer cells depends on autocrine release of tumor necrosis factor α (TNFα); however, potential mechanisms of resistance remain unknown. Here, we investigated the molecular profile and cytotoxic responsiveness of a diverse panel of 51 cancer cell lines to combinations of a dimeric SMC (AEG40730), death ligand TNFα, and tumor necrosis factor-related apoptosis-inducing ligand. Synergy was seen in combination with death receptor agonists in some cells, although single-agent activity was limited to a fewsensitive lines. Unexpectedly, the majority of cell lines resistant to combinations of SMC-AEG40730 and death ligands expressed caspase-8, FADD, RIP1, and ligand receptors necessary for apoptosis execution. Furthermore, TNFα-mediated ubiquitination of RIP1 was repressed by SMC-AEG40730 treatment, leading to the formation of the proapoptosis complex II. However, in resistant cancer cells, SMC-AEG40730 repressed TNFα-mediated c-jun-NH2-kinase activation and the levels of caspase-8 inhibitor c-FLIP were persistently elevated, in contrast to SMC-responsive cancer cells. Importantly, the silencing of c-FLIP restored SMC sensitivity in previously resistant cancer cells by allowing ligand-mediated activation of caspase-8 and caspase-3 to proceed. Together, these results provide mechanistic insight into the action of SMCs, demonstrating that the deciphering of the relevant molecular signature in cancer cells leads to the prediction of cancer cell responsiveness to SMC treatment. Furthermore, a majority of resistant cancer cells were sensitized to SMC-AEG40730 and TNFα by down-regulating c-FLIP, suggesting novel approaches in the use of SMCs and c-FLIP antagonists in treating cancer. [Cancer Res 2009;69(19):7729–38]
Genomic Analysis of Drosophila melanogaster Telomeres: Full-length Copies of HeT-A and TART Elements at Telomeres
Authors: José P. Abad, Beatriz de Pablos, Kazutoyo Osoegawa, Pieter J. de Jong, Antonia Martín-Gallardo, Alfredo Villasante
Journal: Molecular Biology and Evolution (2004)

The repetitive nature of heterochromatin hampers its analysis in general genome-sequencing projects. Specific studies are needed to extend the sequence into telomeric and centromeric heterochromatin. Drosophila telomeres lack the telomerase-generated repeats that are characteristic of other eukaryotic chromosomes. Instead, they consist of tandem arrays of HeT-A and TART elements. Herein, we present the genomic organization of the telomeres in the isogenic strain (y; cn bw sp) that was used for the Drosophila melanogaster sequencing project. The data indicate that the canonical features of telomere organization are widely conserved in evolution. In addition, we have identified full-length elements, likely competent elements, for HeT-A and TART.
Bone marrow transplantation across major histocompatibility barriers. V. Protection of mice from lethal graft-vs.-host disease by pretreatment of donor cells with monoclonal anti-Thy-1.2 coupled to the toxin ricin.
Authors: D A Vallera, R J Youle, D M Neville, J H Kersey
Journal: The Journal of Experimental Medicine (1982)

A new method has been devised to eliminate T cells from murine bone marrow grafts across major histocompatibility barriers and thus prevent graft-vs.-host disease (GVHD). The method utilizes a monoclonal antibody directed at the Thy-1.2 antigen but is complement independent. To make anti-Thy-1.2 toxic, the antibody is covalently linked to the toxin ricin. Ricin ordinarily binds, enters, and kills cells through receptors containing galactose. The hybrid protein, anti-Thy-1.2-ricin, can enter and kill cells via the Thy-1.2 receptor. In the presence of lactose the usual entry route for ricin is largely blocked and the hybrid is shown to be a highly selective reagent that is T cell specific in its inhibition of mitogen-stimulated splenocytes. We have used a model of severe and fatal GVHD where BALB/c splenocytes and bone marrow cells are given to irradiated C57BL/6 recipients. Over 90% of these mice die by day 70, exhibiting signs of GVHD. When donor cells are pretreated with 0.5 microgram/ml of anti-Thy-1.2-ricin plus 200 mM lactose before injection, 10 of 11 animals survive through day 70 without signs of GVHD. These studies demonstrate that ricin linked to monoclonal antibodies may have utility related to the prevention of GVHD in human bone marrow transplantation.