tbuckley/cabot-search huggingface dataset:
AB1020 Mortality under low-impact fractures of the proximal femur in older age group
Authors: J. Averkieva, T. Raskina
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The Mediko-social importance of an osteoporosis is defined by its consequences – crises of vertebras and bones of the peripheral skeleton, causing high indicators of a lethality among persons of the senior age group. <h3>Objectives</h3> To examine outcomes in low-traumatic fractures of the proximal femur in older age groups in Kemerovo during the observation periods: 0-6, 7-12, 13-24 months. <h3>Methods</h3> Mortality among 432 residents of Kemerovo at the age of 50 and older who were seen at trauma departments from 01 January 2004 to December 31, 2008 has been analyzed. The information about fractures and their outcome was obtained according to the medical records of specialized trauma departments (medical history, dropped out patients’ maps of the hospital), the telephone survey, registration data of registry offices. <h3>Results</h3> Analysis of women mortality with the following results: for 6 months 73 (22,25%) of 328 women died, during the period 7-12 months - 31 (12,15%) of 255 patients, between 13-24 months - 36 (16,07%) of the 224 remaining under the supervision. It is noted that mortality with women was significantly higher during the first 6 months after injury than after 7-12 months (χ<sup>2</sup>=6,3; p&lt;0.001) and after 13-24 months (χ<sup>2</sup>=2,21; p=0,04). No significant differences in the comparative analysis of mortality rates with women during periods of 7-12 months and 13-24 months (p=0,21). Men’s mortality in the study period of observation was as follows: for the first 6 months 22 patients died (21,15%) of 104 ones, during the period 7-12 months mortality increase was 11 (13,41%) of 82 patients, during the period 13-24 months - 11 of 71 (15,49%) patients. No significant differences in all the periods of observation have been received: for 0-6 months and 7-12 months (χ<sup>2</sup>=1,2; p=0,17) for 7-12 months and 13-24 months (χ<sup>2</sup>=0,46; p=0.7) for 0-6 months and 13-24 months (χ<sup>2</sup>=0,9; p=0,3). <h3>Conclusions</h3> Thus, these results indicate significantly higher mortality during the first 6 months after hip fracture with women. No statistically significant differences in mortality among men are revealed. <h3>Disclosure of Interest</h3> None Declared
S123 Increased risk of upper respiratory infection with addition of intermittent bolus-dose vitamin D supplementation to a daily low-dose regimen
Authors: AR Martineau, Y Hanifa, RL Hooper, KD Witt, M Patel, A Syed, DA Jolliffe, PM Timms, Z Balayah, N Stevens, DA Clark, S Eldridge, N Barnes, CJ Griffiths
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Meta-analysis of clinical trials of vitamin D supplementation for the prevention of acute respiratory infection (ARI) shows a protective effect in the general population, but there is controversy regarding the optimal dosing regimen. Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against ARI are lacking. <h3>Methods</h3> We conducted a double-blind cluster-randomised placebo-controlled trial of high- vs. low-dose vitamin D supplementation in residents and staff of sheltered accommodation schemes in London, UK. 108 schemes were allocated to receive the intervention (vitamin D<sub>3</sub> 2.4 mg 2-monthly + 10 μg daily for residents; 3 mg 2-monthly for staff) or control (vitamin D<sub>3</sub> 10 μg daily for residents, nil for staff) over the course of one year. The primary endpoint of the trial was time from first dose of study medication to date of first ARI, determined by a validated acute respiratory symptom score recorded prospectively in a symptom diary. Secondary outcomes included time to first upper / lower respiratory infections (URI/LRI) and mean serum 25-hydroxyvitamin D (25[OH]D) concentration. <h3>Results</h3> 240 participants were included in the intention-to-treat analysis (137 participants in 54 schemes allocated to intervention, mean baseline 25[OH]D 43.8 nmol/L vs. 103 participants in 54 schemes allocated to control, mean baseline 25[OH]D 43.8 nmol/L). Median time to ARI was 203 days in the intervention arm and 227 days in the control arm (adjusted HR 1.18, 95% CI 0.80 to 1.74, p = 0.42). Allocation to the intervention arm of the trial was associated with increased risk of URI (adjusted HR 1.48, 95% CI 1.02 to 2.16, p = 0.04), but not with altered risk of LRI (adjusted HR 1.12, 95% CI 0.73 to 1.70, p = 0.61). Mean serum 25(OH)D concentration at 1 year was 84.8 nmol/L vs. 58.5 nmol/L in intervention vs. control arms (p &lt; 0.0001). <h3>Conclusions</h3> Addition of intermittent bolus-dose vitamin D supplementation to a daily low-dose regimen improved vitamin D status in older adults and their carers, but it did not influence risk of ARI, and was less effective at preventing URI.
A1.4 Inflammatory microenvironment of rheumatoid and osteoarthritic joint affects immunomodulatory activity of adipose-derived mesenchymal stem cells
Authors: U Skalska, E Kontny
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Adipose-derived mesenchymal stem cells (ASCs) have immunomodulatory properties, but their activity is dependent on signals provided by local microenvironment. ASCs administration in rheumatoid arthritis (RA) did not bring consistent results, while in osteoarthritis (OA) it has beneficial effects. It is likely that proinflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs (RA-ASCs) and osteoarthritic ASCs (OA-ASCs) isolated from infrapatellar fat pad of the knee joint have been analysed. <h3>Materials and methods</h3> Infrapatellar fat pads were obtained from 29 RA and 12 OA patients undergoing total knee joint replacement surgery. Then, ASCs were isolated accordingly to routinely applied procedure. ASCs were treated or not with IFNγ or TNF. The expression of indoleamine 2,3-dioxygenase and heme oxygenase 1 mRNA was measured using quantitative PCR, while ASCs secretory potential was assessed by specific ELISAs. Rheumatoid synovial fibroblasts (RA-FLS) or peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured in ASC-conditioned media or co-cultured with ASCs. Next, cytokines secretion and cells proliferation were measured using ELISAs and bromodeoxyuridine/<sup>3</sup>H-thymidine proliferation assays, respectively. <h3>Results</h3> RA- and OA-ASCs activity <i> in vitro </i>is comparable, nonetheless some differences in spontaneous secretory activity and heme oxygenase 1 mRNA expression have been observed. Unstimulated RA- and OA-ASCs slightly inhibited PBMCs proliferation and induced IL-10 secretion but increased IL-17A production and failed to suppress release of other proinflammatory factors (TNF, IFNγ, RANTES) by PBMCs. Under TNF stimulation, RA- and OA-ASCs up-regulated IL-6 and MMP-3 secretion in RA-FLS cultures and IL-17A release by PBMCs. ASCs treatment with IFNγ or TNF did not intensify their anti-inflammatory activity. <h3>Conclusions</h3> Our study demonstrates that immunosuppressive function of RA- and OA-ASCs derived from infrapatellar fat pad is impaired. Possibly, it is due to the localisation of ASCs in the site of inflammation. Moreover, TNF triggers proinflammatory properties of ASCs which indicates that when administered to the rheumatoid joint, ASCs may shift from an anti-inflammatory to proinflammatory phenotype. <h3>Acknowledgements</h3> This work was supported by the Polish National Science Centre (grant no. 2011/01/N/NZ5/00932) and by the European Union funds (European Social Fund, Human Capital Programme).
Abstract SY11-02: The role of the histone deacetylase SIRT6 in glucose homeostasis and cancer
Authors: Raul Mostoslavsky, Carlos Sebastian, Lei Zhong, Sofia Giacosa, Deborah Toiber
Journal: Cancer Research (2011)

Abstract Efficient glucose metabolism is critical for maintaining cellular viability. Under normal nutrient and oxygen conditions, glucose is converted to pyruvate, entering the mitochondria for oxidative phosphorylation and ATP production. Under hypoxia or nutrient stress, metabolism is switched to glycolysis, increasing lactate production and reducing mitochondrial respiration. This switch is critical to maintain cells during periods of starvation or hypoxia; furthermore, recent studies indicate that modulating this switch proved beneficial under chronic glucose imbalance, such as in patients with type II diabetes, and it also plays a critical role in cancer metabolism, as defined by Otto Warburg decades ago. Little is known whether chromatin plays a role in carbohydrate flux. The yeast Sir2 protein is an NAD-dependent histone deacetylase that senses the metabolic status of the cell and functions as a chromatin silencer to promote lifespan and genomic stability. Recently, we discovered that the mammalian SIRT6 is a chromatin factor that influences glucose metabolism and DNA repair. In mice, SIRT6-deficiency provokes a profound and lethal hypoglycemia which culminates in accelerated death. At the cellular level, SIRT6 inactivation leads to increased cellular glucose uptake, higher lactate production and decreased mitochondrial activity. Our results indicate that SIRT6 directly regulates expression of several key glycolytic genes. In this context, SIRT6 functions at chromatin to attenuate a Hif1α transcriptional nutrient response. SIRT6 co-represses Hif1α, acting as a histone H3 lysine9 (H3K9) deacetylase to inhibit expression of Hif1α-target gene promoters (Zhong et al, 2010). In the absence of SIRT6, H3K9 acetylation is enhanced in these promoters, triggering a Hif1α-dependent glycolytic switch, a response that appears critical in order to maintain cells under conditions of nutrient stress. In this context, our new studies indicate that this “glycolytic switch” observed in the absence of SIRT6 provides a growth advantage in the context of tumorigenesis. Potential mechanistic implications will be further discussed. Zhong, L., D'Urso, A., Toiber, D., Sebastian, C., Henry, R.E., Vadysirisack, D.D., Guimaraes, A., Marinelli, B., Wikstrom, J.D., Nir, T., Clish, C.B., Vaitheesvaran, Iliopoulos, O., B., Kurland, I., Dor, Y., Weissleder, R., Shirihai, O.S., Ellisen, L., Espinosa, J.M., and Mostoslavsky, R. (2010). The histone deacetylase SIRT6 regulates glucose homeostasis via Hif1a. Cell, 140, 280-293. 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 SY11-02. doi:10.1158/1538-7445.AM2011-SY11-02
Abstract 4374: Identification of novel, biologically relevant, G-quadruplexes formed within the critical promoter of kRAS as promising molecular targets.
Authors: Chi-Fan Hockings, Kristen M. Greer, Tracy A. Brooks
Journal: Cancer Research (2013)

Abstract To date, kRAS is one of, if not the, most established oncogenic anomalies identified. It is either upregulated or mutationally activated in a variety of cancers, most notably pancreatic adenocarcinoma, non-small cell lung and colon cancers. Pancreatic cancer carries the highest mortality rate of all cancers, with only a 3-6 month median survival, and a 5-year survival of &amp;lt;5%. Lung and colon cancers harboring a mutant kRAS are associated with a worsened prognosis and shorter disease-free survival, and such mutations are independent factors for poor prognosis. To date no attempts to modulate kRAS activity, localization, or signaling have produced clinically active moieties; there is a desperate need for new, kRAS-focused therapeutics. Various silencing technologies have demonstrated that decreasing kRAS expression is sufficient to produce cancer cell kill, and the presented works describe a novel target to downregulate kRAS expression - secondary structures within the proximal promoter, which contains a unique string of G-rich DNA. Negative superhelicity induced by transcription results in this region opening up to form unique secondary structures called G-quadruplexes (G4s). These G4s most often act as silencer elements, forming globular structures that mask binding sites for transcriptional factors, allowing for specific molecular targeting by small molecule drugs, modulating transcription, and protein expression. The G-rich region of the kRAS promoter is extensive, containing three separate putative G4-forming regions. Initial works described the near G4 as a unique ‘kinked’ structure, as well as described two compounds that stabilize different isoforms of this structure, but do not appear to contribute much to the transcriptional control of kRAS. Further elucidation of promoter activity has highlighted new, and more biologically important, G4s existing more distally from the transcriptional state site. Stabilization of this region in a plasmid system significantly decreases luciferase expression, and the mid-G4-forming region forms several stable, complex, structures. These formations have been examined by EMSA, polymerase stop, and footprinting methods. From these data, the elucidated predominant structures are currently the target of further studies with the ultimate goal of describing a new molecular structure, and its dynamic regulation, for future drug development. Citation Format: Chi-Fan Hockings, Kristen M. Greer, Tracy A. Brooks. Identification of novel, biologically relevant, G-quadruplexes formed within the critical promoter of kRAS as promising molecular targets. [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 4374. doi:10.1158/1538-7445.AM2013-4374
Abstract SY35-03: Gene expression and epigenetic programs in leukemia stem cell development
Authors: Scott A. Armstrong
Journal: Cancer Research (2012)

Abstract Acute myelogenous leukemia stem cells (LSC) are the subset of leukemia cells capable of extensive self-renewal and maintenance of leukemia. We are interested in the mechanisms of leukemia development as they relate to activation and maintenance of gene expression programs by epigenetic pathways responsible for deregulated self-renewal in leukemia. We have demonstrated that oncogenic fusion proteins can activate a self-renewal associated gene expression program when expressed in myeloid progenitor cells that normally have limited self-renewal capabilities. Detailed characterization of LSC from multiple different mouse leukemias has shown that LSC are most similar to differentiating myeloid cells that express a limited hematopoietic stem cell (HSC) associated signature. Detailed analysis of the gene expression data from normal HSC and progenitors as compared to LSC identified the Wnt/β-catenin pathway as potentially important for acute myeloid leukemia LSC, and we have subsequently validated this pathway as critical using conditional mouse models. We are continuing to assess the gene expression programs subverted during the transition from normal HSC and progenitor cells to LSC and are comparing these data to genome wide epigenomic analyses to determine which specific epigenetic programs are required for leukemia stem cell maintenance. Identification of epigenetic pathways required to maintain leukemia self-renewal should provide new targets for novel therapeutic approaches. 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 SY35-03. doi:1538-7445.AM2012-SY35-03
Abstract 3964: Transforming growth factor-beta dependent regulation in breast cancer progression
Authors: Hye Ok Kim, Junkyu Song, Chang Hoon Cho, Kyung-sik Yoon
Journal: Cancer Research (2010)

Abstract Transforming growth factor-ß (TGF-ß) has a wide range of biologic functions such as the regulation of cell growth, differentiation, and immunologic response in various types of cells. The involvement of TGF-ß in the pathogenesis of breast cancer has been proposed based on its capacity to stimulate the production of extracellular matrix (ECM) proteins and to regulate their metabolism. Induction of plasminogen activator inhibitor-1 (PAI-1) by TGF-ß may contribute to the degradation of extracellular matrix during cancer invasion by decreasing the adhesive strength of cells. Thus, it is important to clarify the mechanism of TGF-ß-induced PAI-1 production. Several polymorphisms have been described in the PAI-1 gene. We examined the influence of the G/A (−844) and 4G/5G (−675) polymorphisms in the promoter region on TGFß-induced PAI-1 expression by breast cancer cells (MDA-MB231, MCF7). The genotype of breast cancer cells was identified by sequencing. TGF-ß-induced PAI-1 mRNA expression was determined by real time polymerase chain reaction (PCR). Activation of MAPKs and Smad proteins was evaluated by an immunoblot analysis. The activities of PAI-1 promoter were measured by a luciferase reporter assay. TGF-ß increased PAI-1 expression in a genotype-dependent manner, higher values observed for MDA-MB231 (4G/4G, A/A) compared with MCF7 (5G/5G, G/G). These results suggest that regulation by TGF-ß influences the PAI-1 polymorphism-dependent expression in breast cancer cells. Analysis of PAI-1 genotype may help identifying subgroups of breast cancer risk. 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 3964.
Abstract 3641: The DNA repair protein hABH2 mediates temozolomide resistance in human glioblastoma cells
Authors: Tor-Christian A. Johannessen, Lars Prestegarden, Berit B. Tysnes, Rolf Bjerkvig
Journal: Cancer Research (2010)

Abstract Background and Purpose: Glioblastoma multiforme is the most malignant and frequent primary brain tumour in adults. Current treatment remains insufficient as these tumours display a diffuse infiltrative growth pattern and tend to recur despite extensive debulking surgery followed by radio- and chemotherapy. The methylating agent temozolomide is at present the cornerstone of glioblastoma chemotherapy. However, several independent DNA repair mechanisms can restore the integrity of methylated DNA bases, and thus contribute to temozolomide resistance and subsequent therapy failure. In this work we examined whether human AlkB homologue 2 (hABH2), an oxidative demethylase capable of reversing methyl lesions in DNA, might provoke temozolomide resistance in human glioblastoma cells. Materials and Methods: hABH2 expression was examined in eight established glioma cell lines as well as normal human brain using quantitative real-time PCR. Cells derived from a hABH2 deficient glioblastoma were transfected with a hABH2 plasmid prior to antibiotic selection, and subsequent colonies were screened for hABH2 expression by western blotting. Temozolomide sensitivity was assessed for hABH2 proficient and deficient colonies using a tetrazolium salt assay after 96 hours of drug incubation. Results: mRNA levels of hABH2 were generally 2-4 fold higher in the established cell lines compared to normal human brain. Furthermore, hABH2 overexpressing glioblastoma cells were significantly more resistant to temozolomide than hABH2 deficient cells derived from the same patient. Conclusions: Our results show that hABH2 is expressed at high levels in glioma cells, and that overexpression of this protein mediates temozolomide resistance in vitro. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3641.
1408 IRREVERSIBLE ELECTROPORATION FOR THE TREATMENT OF EARLY-STAGE HEPATOCELLULAR CARCINOMA. A PROSPECTIVE MULTICENTER PHASE 2 STUDY ASSESSING SAFETY AND EFFICACY
Authors: J. Bruix, F. Izzo, L. Crocetti, V. Vilgrain, M. Abdel-Rehim, L. Bianchi, J. Ricke, M. Pech, R. Lencioni
Journal: Journal of Hepatology (2012)
Effect of Hypophosphatemia on Diaphragmatic Contractility in Patients with Acute Respiratory Failure
Authors: Michel Aubier, Daniéle Murciano, Yann Lecocguic, Naïma Viires, Yves Jacquens, Pierre Squara, René Pariente
Journal: New England Journal of Medicine (1985)

We studied the effects of hypophosphatemia on diaphragmatic function in eight patients with acute respiratory failure who were artificially ventilated. Their mean serum phosphorus level was 0.55 +/- 0.18 mmol per liter (normal value, 1.20 +/- 0.10). The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure generated at functional residual capacity during bilateral supramaximal electrical stimulation of the phrenic nerves. Diaphragmatic function was evaluated in each patient before and after correction of hypophosphatemia, which was achieved by administration of 10 mmol of phosphorus (as KH2PO4) as a continuous infusion for four hours. After phosphate infusion, the mean serum phosphorus level increased significantly (1.33 +/- 0.21 mmol per liter, P less than 0.0001). The increase in serum phosphorus was accompanied by a marked increase in the transdiaphragmatic pressure after phrenic stimulation (17.25 +/- 6.5 cm H2O as compared with 9.75 +/- 3.8 before phosphate infusion, P less than 0.001). Changes in the serum phosphorus level and transdiaphragmatic pressure were well correlated (r = 0.73). These results strongly suggest that hypophosphatemia impairs the contractile properties of the diaphragm during acute respiratory failure, and they emphasize the importance of maintaining normal serum inorganic phosphate levels in such patients.
Huge Tumor Thrombus of Chondrosarcoma on FDG PET/CT
Authors: Cheng-Nan Hsu, Hui-Yi Chen, Yu-Chin Wu, Chun-Fan Yang, Te-Chun Hsieh
Journal: Clinical Nuclear Medicine (2011)

A 24-year-old woman presented with progressive pain in the left groin and left buttock for 4 months. The whole-body FDG PET/CT and MRI of the pelvis revealed a left pelvic mass and venous thrombosis in the left common iliac vein, inferior vena cava, and right atrium. Chondrosarcoma with venous tumor invasion of the inferior vena cava to the right atrium was documented surgically.
Expression patterns of the JEM-1 gene in normal and tumor cells: ubiquity contrasting with a faint, but retinoid-induced, mRNA expression in promyelocytic NB4 cells
Authors: J-H Tong, X Fant, E Duprez, G Benoit, CC Uphoff, HG Drexler, JC Pla, E Lofvenberg, M Lanotte
Journal: Leukemia (1998)
COMPARISON OF GFR DETERMINATION BY I-125 IODOTHALAMATE, TC-99M SCINTIGRAPHY AND TC-99M DTPA CLEARANCE FROM BLOOD.
Authors: Kathryn A. Morton, Jeff Goates, Fred Datz, Anthony Scuderi, Jerry Handy
Journal: Clinical Nuclear Medicine (1988)

Morton, Kathryn A.; Goates, Jeff; Datz, Fred; Scuderi, Anthony; Handy, Jerry Author Information