tbuckley/cabot-search huggingface dataset:
EG-13 * GENOME-WIDE METHYLATION ANALYSIS IDENTIFIES GENOMIC DNA DEMETHYLATION DURING MALIGNANT PROGRESSION OF GLIOMAS
Authors: K. Saito, A. Mukasa, G. Nagae, K. Aihara, R. Otani, S. Takayanagi, M. Omata, S. Tanaka, J. Shibahara, M. Takahashi, T. Momose, T. Shimamura, S. Miyano, Y. Narita, K. Ueki, R. Nishikawa, M. Nagane, H. Aburatani, N. Saito
Journal: Neuro-Oncology (2014)

Low-grade gliomas often undergo malignant progression, and these transformations are a leading cause of death in patients with low-grade gliomas. However, the molecular mechanisms underlying malignant tumor progression are still not well understood. Recent evidence indicates that epigenetic deregulation is an important cause of gliomagenesis; therefore, we examined the impact of epigenetic changes during malignant progression of low-grade gliomas. Specifically, we used the Illumina Infinium Human Methylation 450K BeadChip to perform genome-wide DNA methylation analysis of 120 gliomas and four normal brains. This study sample included 25 matched-pairs of initial low-grade gliomas and recurrent tumors (temporal heterogeneity) and 20 of the 25 recurring tumors recurred as malignant progressions, and one matched-pair of newly emerging malignant lesions and pre-existing lesions (spatial heterogeneity). Analyses of methylation profiles demonstrated that most low-grade gliomas in our sample (43/51; 84%) had a CpG island methylator phenotype (G-CIMP). Remarkably, approximately 50% of secondary glioblastomas that had progressed from low-grade tumors with the G-CIMP status exhibited a characteristic partial demethylation of genomic DNA during malignant progression, but other recurrent gliomas showed no apparent change in DNA methylation pattern. Interestingly, we found that most loci that were demethylated during malignant progression were located outside of CpG islands. The information of histone modifications patterns in normal human astrocytes and embryonal stem cells also showed that the ratio of active marks at the site corresponding to DNA demethylated loci in G-CIMP-demethylated tumors was significantly lower; this finding indicated that most demethylated loci in G-CIMP-demethylated tumors were likely transcriptionally inactive. A small number of the genes that were upregulated and had demethylated CpG islands were associated with cell cycle-related pathway. In summary, we demonstrated that characteristic DNA demethylation occurred during malignant progression of a subset of low-grade gliomas. The mechanisms underlying and consequences of such DNA demethylation should be studied further.
Postoperative Hepatic Necrosis
Authors: E. M. Slater, J. M. Gibson, M. H. M. Dykes, S. G. Walzer
Journal: New England Journal of Medicine (1964)

HEPATIC necrosis in man was first associated with the administration of chloroform in 1895.1 It has also been noted after exposure to carbon tetrachloride,2 , 3 trichloroethylene4 5 6 7 and tribromethanol.8 , 9 Since 1956 another halogenated anesthetic agent, halothane (2-bromo-2-chloro-1,1,1-trifluoroethane), has gained great popularity because of many desirable pharmacologic and physical properties.10 , 11 However, isolated cases of jaundice, and of deaths due to hepatic failure after the administration of this agent, have been reported.12 13 14 15 16 17 18 19 20 21 22 Once again the association between hepatic necrosis and the administration of a halogenated hydrocarbon has been noted. This study was initiated to determine the incidence of hepatic necrosis after the administration of . . .
Ante-Natal Screening and Abortion for Fetal Abnormality, by Ed David Paintin
Authors: S. W G Derbyshire
Journal: BMJ (1997)

Ed David Paintin: Birth Control Trust, £20, pp 96 ISBN 0 906 233 37 2

Based on the proceedings of a one day symposium, this book is an excellent reminder that it is possible to have a non-hysterical discussion about abortion. The aim of the symposium was to debate the clinical and ethical issues involved in screening for fetal abnormality, to clarify good practice in respect of late abortion for fetal abnormality, and to discuss the problems of providing a service sympathetic to women.

The book provides many useful facts and good advice about the practicalities of providing an abortion service. For instance, a current failing is the lack of services for women who have normal pregnancies. In developed countries many pregnant women have antenatal tests, with most turning up nothing …
Genetic Clues About Colon Cancer Reshape Treatment Approaches
Authors: D. Holzman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Genetic Clues About Colon Cancer Reshape Treatment Approaches Get access D. Holzman D. Holzman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 10, 17 May 1995, Pages 708–709, https://doi.org/10.1093/jnci/87.10.708 Published: 17 May 1995
A8.2 Oral administration of bovine milk-derived extracellular vesicles diminishes cartilage pathology in two arthritis models
Authors: OJ Arntz, BCH Pieters, MC de Oliveira, MB Bennink, van Lent Plem, PM van der Kraan, MI Koenders, FAJ van de Loo
Journal: Annals of the Rheumatic Diseases (2015)

<h3></h3> Development of rheumatoid arthritis (RA) is associated with environmental factors and several studies show a connetion with diet. Recently, exosomes are identified in both bovine and human breast milk. Exosomes are small (30–200 nm) membrane-derived extracellular vesicles that carry immunoregulatory microRNAs, proteins and lipids, and mediate intercellular communication. In this study, we investigated the effect of oral intake of bovine milk-derived extracellular vesicles (BMEVs) on spontaneous polyarthritis in IL-1Ra deficient mice and on collagen-induced arthritis (CIA) in DBA1/J mice. BMEVs were isolated from skimmed milk by ultracentrifugation and characterised by nanoparticle tracking analysis, electron microscopy, anti-CD63 staining, and PCR. BMEVs were labelled with PKH-67 to determined the uptake by cells using FACS and confocal microscopy. TGFb levels were measured with a CAGA-fLuc reporter construct. Naïve T cells were cultured for 5 days with an inflammatory cocktail in the presence of milk exosomes, to induce Th17 differentiation as assessed by RORgT and IL-17 mRNA expression. In IL-1Ra<sup>-/-</sup> mice, BMEVs were administered daily by oral gavage starting at week 5 till 15 after birth and arthritis was scored macroscopically. In CIA, mice received BMEVs via their drinking water starting 1 week before immunisation till day 40. Arthritis was scored macroscopically and on histology. To determine the effect on immunity, serum IgG levels were measured by ELISA, T-cell specific gene expression (T-bet, RORgT, GATA-3) in LPS stimulated splenocytes by Luminex and RT-qPCR. The BMEV particle size was around 120 nm and expressed the exosome markers tetraspanin CD63, miRNA’s (miR-let-7a, -16, -30a, -92a, -223), and milk specific beta-casein and beta-lactoglobulin mRNA. Acidification, up to gastric acid level (pH 2) left the BMEVs intact, and did not alter their inhibitory effect on NFkB-activation. Active TGFb was detected on BMEVs and incubation of naïve T cells with BMEVs induced significant Th17 differentiation to a similar extent as TGFb. However, BMEVs treatment of mice showed a delayed onset of arthritis in both the IL-1Ra<sup>-/-</sup> and CIA model. Diminished cartilage pathology and bone marrow inflammation was observed in both models. BMEVs also reduced the circulation levels of MCP1 and IL-6 levels and their production by splenic cells. In BMEV treated CIA, circulating anti-collagen type II IgGa level was reduced and this was accompanied by reduced splenic Th1 and Th17 numbers. Bovine milk-derived extracellular vesicles are bioactive, probably can withstand the harsh conditions of the gut, and oral delivery ameliorates disease in two RA models.
The Benefit of Exchanging Donor Kidneys among Transplant Centers
Authors: Gerhard Opelz
Journal: New England Journal of Medicine (1988)

Whether kidneys from cadaver donors should be exchanged among transplant centers is controversial. We analyzed the effect of matching for HLA-B and HLA-DR antigens on graft survival in patients treated with cyclosporine. The results in 9369 recipients of kidneys obtained and transplanted in the same center were compared with those in 5553 recipients of kidneys shipped from one center to another. In both patient subgroups, the association of HLA matching with graft survival was statistically significant (P<0.0001). Moreover, well-matched exchanged kidneys survived better than poorly matched locally transplanted kidneys. Among patients receiving their first cadaver transplant, graft survival at one year was 13 percentage points higher (P<0.0001) in exchanged kidneys without mismatches than in local kidneys with four mismatches. Among patients receiving their second transplant, graft survival was 21 percentage points higher (P<0.001). Kidney preservation for up to 48 hours did not affect graft survival significantly. Transplantation of poorly matched local kidneys preserved with a short period of cold ischemia (<24 hours) had significantly lower rates of success than did transplantation of well-matched exchanged kidneys with a longer period of cold ischemia (up to 48 hours) (P<0.0001). Our data indicate that the exchange of cadaver kidneys among transplant centers to obtain grafts with better HLA matching can improve the success rate of renal transplantation. (N Engl J Med 1988; 318:1289–92.)
SP0072 Markers of premature mortality: Chronic symptoms
Authors: G.T. Jones
Journal: Annals of the Rheumatic Diseases (2013)

A number of studies have examined the relationship between chronic (musculoskeletal) pain and mortality. Some have shown increases in all-cause, cancer-related and cardio-respiratory mortality. However, results are equivocal and others have reported null or non-significant effects. This lecture (a) will summarise the evidence in this field; (b) will present some recent data suggesting a possible gender-specific effect; and (c) will review recent papers examining possible mechanisms for such a relationship – focusing on modifiable lifestyle factors such as diet and lifestyle. <h3>Disclosure of Interest</h3> None Declared
A1.14 Synovial macrophages promote TGF-β signalling but protect against influx of S100A8/S100A9-producing cells after intra-articular injections of oxidised low-density lipoproteins
Authors: W de Munter, EJW Geven, AB Blom, B Walgreen, MMA Helsen, LAB Joosten, J Roth, T Vogl, FAJ van de Loo, MI Koenders, WB van den Berg, PM van der Kraan, PLEM van Lent
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> LDL in inflamed synovium is oxidised and taken-up by macrophages, leading to an activated macrophage phenotype. In this study, we investigate whether injection of oxLDL directly into a murine knee joint induces joint pathology and elucidate the role of synovial macrophages in that process. <h3>Materials and Methods</h3> Synovium was obtained from end-stage OA patients. Murine knee joints were injected five consecutive days with oxLDL, LDL, or vehicle (PBS). This procedure was repeated in mice depleted of synovial lining macrophages by intraarticular injection of clodronate liposomes seven days prior to the consecutive injections. Joint pathology was investigated by immunohistochemistry, flow cytometry (FCM) and synovial RNA expression and protein production. <h3>Results</h3> Synovial macrophages and fibroblast of OA patients showed extensive accumulation apolipoprotein B, the main protein present in LDL and oxLDL. Multiple injections of oxLDL in murine knee joints significantly increased TGF-β activity in synovial wash-outs, but did not induce catabolic or inflammatory processes. In contrast, repeated injections of specifically oxLDL in macrophage-depleted knee joints led to increased synovial thickening. Furthermore, protein and RNA levels of CCL2 and CCL3 were significantly upregulated in macrophage-depleted joints after oxLDL injections and FCM-analyses revealed increased presence of monocytes and neutrophils in the synovium, which was confirmed by immunohistochemistry. Also protein levels of S100A8/A9 were significantly increased in synovial wash-outs of oxLDL-injected joints, as was expression of aggrecanase-induced neo-epitopes. Interestingly, no raise in active TGF-β was measured in macrophage-depleted joints. <h3>Conclusions</h3> Synovial macrophages promote anabolic processes after oxLDL injections. In absence of synovial macrophages, however, oxLDL induces production of pro-inflammatory mediators and aggrecanase activity in combination with increased influx of monocytes and neutrophils.
Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: a randomized phase III study
Authors: W. Jacot, N. Firmin, L. Roca, D. Topart, S. Gallet, A. Durigova, S. Mirr, L. Abach, S. Pouderoux, V. D'Hondt, J.P. Bleuse, P.J. Lamy, G. Romieu
Journal: Annals of Oncology (2016)
FRI0178 Estimated Medical Expenditures among Patients with Rheumatoid Arthritis Undergoing Treatment with Tofacitinib, an Oral Janus Kinase Inhibitor
Authors: R. Rendas-Baum, M. Kosinski, A. Singh, C. Mebus, B. Wilkinson, R. Riese, G. Wallenstein
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Phase (P) 3 studies demonstrated tofacitinib is effective and has a manageable safety profile at both 5 and 10 mg twice-daily (BID) doses. <h3>Objectives</h3> To assess, using post-hoc analyses of P3 data, whether active treatment could affect monthly medical expenditure (MME) compared with placebo. <h3>Methods</h3> Data from patients with an inadequate response (IR) to methotrexate (MTX) or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg BID, or adalimumab (ORAL Standard only), in combination with methotrexate, were assessed from two randomised P3 studies (ORAL Standard, NCT00853385 [MTX-IR] and ORAL Step, NCT00960440 [TNFi-IR]). Differences across treatment groups in estimated MME were evaluated using a longitudinal model. A total of three models were run for each study, each with one of the following variance–covariance structures: 1) unstructured, 2) auto-regressive of order 1 and 3) compound symmetry. The final variance–covariance structure was selected based on Akaike9s Information Criteria. <h3>Results</h3> Estimated MME by treatment group for MTX-IR in ORAL Standard is presented in Fig. 1a. By Month 1 mean MME was significantly lower in the active treatment groups when compared with placebo; the MME was decreased −$89 for the tofacitinib 10 mg BID group compared with an increase of $70 in both the tofacitinib 5 mg BID and adalimumab groups. During the placebo-controlled phase of ORAL Step, estimated MME by treatment group for TNFi-IR decreased from baseline to Month 1. Between Month 1 and Month 3 the MME of the placebo group increased but declined further in the two active tofacitinib treatment groups (Fig. 1b). By Month 3 the reduction in MME was over $100 greater in each of the two tofacitinib groups when compared with placebo. <h3>Conclusions</h3> Tofacitinib is expected to have a positive impact on medical expenditure over time compared with placebo. <h3>Acknowledgements</h3> Editorial assistance was provided by Mark Walker PhD, of Complete Medical Communications and funded by Pfizer Inc. <h3>Disclosure of Interest</h3> R. Rendas-Baum: None declared, M. Kosinski: None declared, A. Singh Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., C. Mebus Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., B. Wilkinson Shareholder of: Pfizer Inc., Employee of: fizer Inc., R. Riese Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., G. Wallenstein Shareholder of: Pfizer Inc., Employee of: Pfizer Inc. <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2476
FRI0149 Nocturnal hypertension in ra: a possible association with cardiovascular events
Authors: K. Hamamoto, S. Yamada, M. Yoda, K. Yoda, M. Tsuda, K. Okamoto, H. Goto, M. Inaba
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although cardiovascular mortality is increased in RA patients relative to the general population, the reasons for high prevalence of cardiovascular events in RA patients is not completely understood. On the other hand, nocturnal hypertension is also known as an important independent predictor of cardiovascular events. However, little is known regarding the relationship between nocturnal hypertensionand RA. <h3>Objectives</h3> To examine the association between nocturnal hypertension and RA, and to investigate whether improvement of RA disease activities aftermedical treatment will affect nocturnal hypertension. <h3>Methods</h3> A total of 70 patients with active RA (12 men and 58 women), mean age of 68.5 years, were enrolled. Of these patients, 14 patients were evaluated the change of nocturnal blood pressure before and after RA treatment. Nocturnal hypertension was assessed by 24 hours ambulatory blood pressure monitoring. There are four subtypes of nocturnal hypertension. These subtypes are determined by the value of the degree of nocturnal blood pressure decline(%). It was calculated as 100 × [1−sleep SBP/awake SBP]. In normal subjects, the degree of nocturnal blood pressure decline from 10% to 20% is described as dipper. A variety of abnormal diurnal variation patterns are described with the degree of nocturnal blood pressure decline as follows, &gt;20%: extreme-dippers; &lt;10%: non-dippers; and &lt;0%: risers. <h3>Results</h3> The mean DAS28-ESR level was 5.6 in 70 RA patients and the mean degree of nocturnal blood pressure decline was 4.5%. The distribution of dipping patterns was as follows: extreme-dippers, 2.9%; dippers, 27.1%; non-dippers, 41.4%; and risers, 28.6%. In simple regression analysis, DAS28-ESR level and the degree of nocturnal blood pressure decline were negatively correlated (p = 0.0042, r = -0.343). In multiple regression analysis, significant independent contributors to the degree of nocturnal blood pressure declinewere age(β = -0.342, p = 0.005) and DAS28-ESR (β = -0.297, p = 0.0210). In 14 RA patients, the mean DAS28-ESR level was improved from 6.1 to 4.6 (p &lt;0.001 ) and the mean degree of nocturnal blood pressure decline was elevated from 1.8 to 8.9 (p = 0.022) after RA treatment. <h3>Conclusions</h3> Our data demonstrate that the degree of nocturnal blood pressure decline is blunted in active RA patients. It is suggested that the occurrence of nocturnal hypertension might be one of cardiovascular risk factors in RA patients. <h3>References</h3> Ann Rheum Dis 2005; 64 :1595-601 JAMA 1999; 282: 5 <h3>Disclosure of Interest</h3> None Declared
Abstract 1705: Bioenergetic changes in glycolysis, Kreb's cycle, and glutaminolysis in pancreatic cells treated with mitochondria-targeted cationic drugs.
Authors: Gang Cheng, Jacek Zielonka, Joy Joseph, Balaraman Kalyanaraman
Journal: Cancer Research (2013)

Abstract Human pancreatic ductal adenocarcinoma (PDAC) is an incurable and highly aggressive human cancer. Current chemotherapy provides a slight increase in survival. New therapeutic strategies to treat PDAC are desperately needed. In this study we used a relatively non-toxic mitochondria-targeted cationic nitroxide (Mito-CP) in combination with antiglycolytic agents (2-deoxyglucose, 2-DG) to selectively inhibit pancreatic cancer cell proliferation. We used high-throughput XF24 extracellular flux analyzer and mass spectrometry-based metabolomics approach to investigate cellular bioenergetics changes in pancreatic cancer cells (MiaPaCa-2 and Panc-1 cells). Results indicate that at nanomolar concentrations, Mito-CP alone potently inhibited proliferation of MiaPaCa-2 cells and synergized with 2-DG in inhibiting intracellular ATP levels. In the presence of glycolytic inhibitors, i.e. 2-DG or 3-bromopyruvate, Mito-CP exhibited enhanced toxicity in both pancreatic cell lines. LC-MS-based metabolomics studies indicate that Mito-CP inhibits Kreb's cycle metabolites (citric acid, cis-aconitic and isocitric acids) but significantly enhances intracellular glutamine, alpha-ketoglutarate, succinate, fumarate, and malate. This enhancement is abolished in glutamine-free media. We conclude that strategies to modulate bioenergetic metabolism with relatively non-toxic mitochondria-targeted nitroxides in combination with glycolysis or glutaminolysis inhibitors may provide a novel route for treating patients with PDAC with minimal toxic side effects. Citation Format: Gang Cheng, Jacek Zielonka, Joy Joseph, Balaraman Kalyanaraman. Bioenergetic changes in glycolysis, Kreb's cycle, and glutaminolysis in pancreatic cells treated with mitochondria-targeted cationic drugs. [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 1705. doi:10.1158/1538-7445.AM2013-1705
Acute Suppurative Thyroiditis Due to Foreign Body–Induced Retropharyngeal Abscess Presented as Thyrotoxicosis
Authors: BABINGTON C. K. YUNG, TONY K. L. LOKE, WAI C. FAN, JAMES C. S. CHAN
Journal: Clinical Nuclear Medicine (2000)

Acute suppurative thyroiditis is an uncommon condition. Most patients have preexisting oropharyngeal fistulae. Penetrating oropharyngeal injuries resulting from swallowed foreign bodies provide an acquired channel of infection spreading into the relatively resistant thyroid gland. The authors describe a patient with infective thyroiditis complicating retropharyngeal abscess caused by a chicken bone that perforated the upper esophagus. Transient thyrotoxicosis complicating acute suppurative thyroiditis is very rare. Pertechnetate and Ga-67 scans confirmed extensive inflammation of the thyroid gland and the release of hormones as the cause, as distinct from concurrent Graves' disease. Awareness of this unusual complication is important to avoid inappropriate treatment for hyperthyroid disease.
First International Congress on Metastatic Disease Held
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1988)

First International Congress on Metastatic Disease Held Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 20, 21 December 1988, Page 1594, https://doi.org/10.1093/jnci/80.20.1594 Published: 21 December 1988