tbuckley/cabot-search huggingface dataset:
SAT0222 Investigating the Association Between Rho-Kinase 1 (Rock1) Gene Polymorphisms and Systemic Sclerosis
Authors: Y. Pehlivan, S. Oztuzcu, S. Donmez, F. Alibaz-Oner, G. Yildirim Cetin, S. Yolbas, I. Bozgeyik, N. Yilmaz, M. Ozgen, B. Kisacik, O. N. Pamuk, M. Sayarlioglu, H. Direskeneli, A. Tuncay Demiryurek, A. Mesut Onat
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Systemic sclerosis (SSc, scleroderma) is an inflammatory diseases characterized by vascular abnormalities and fibrosis (1). The role of Rho-kinase in inflammation, in the pathogenesis of vascular structure and fibrosis has been proved with several studies. We aimed to investigate a possible association between <i>ROCK1</i> gene polymorphisms and SSc patients in a Turkish population. <h3>Methods</h3> A total of 284 patients fulfilling the American Collage of Rheumatology criteria on SSc and 284 healthy control subjects with similar age and sex were enrolled to this study. Genomic DNA from the participants was analyzed by a BioMark HD 96.96 dynamic array system (Fluidigm, CA, USA). For calculation of the significance of differences in genotype and allele frequencies, the chi-square test (with Yates’ correction) or Fisher’s exact test was used. The haplotype analysis was performed by using online software program, SHEsis (http://analysis.bio-x.cn/myAnalysis.php). <h3>Results</h3> There was an increase in GG genotype frequencies (9.4% in SSc vs. 3.2% in control) and decrease in GA genotype frequencies (90.6% in SSc vs. 96.8% in control, P=0.004, OR (95%CI) of the <i>ROCK1</i> gene rs112108028 polymorphism. CC genotype and C allele frequencies of the rs111874856 polymorphism were markedly low in cases with SSc (CC, 33.7%, C, 33.7%) when compared to control group (CC, 100.0%, C, 100.0%). TT genotype and T allele were not detected in the control group, whereas these frequencies were found to be high in SSc group (TT, 66.3%, T, 66.3%, P&lt;0.0001). AA (97.8%) genotype and A allele (98.9%) of the rs35996865 polymorphism were significantly more common among SSc group than among controls (AA, 93.9%, A, 95.9%). In the haplotype analysis based on these 3 polymorphisms, four haplotypes (ACA, GCA, ATA and GTA) were found to be significantly associated with SSc, and ATA (27.6%) and GTA (36.2%) haplotypes were present only in patients (P&lt;0.0001). Additionally, no marked association was found between rs1045144 polymorphism and SSc. <h3>Conclusions</h3> This is the first study to investigate the potential association between <i>ROCK1</i> gene polymorphisms and SSc. Our data showed that there is a statistically significant association between <i>ROCK1</i> gene polymorphism and SSc. Moreover, these findings suggest that functional effects of ROCK1 gene can help to understand the pathogenesis of SSc. <h3>Acknowledgements</h3> <i>This study has been funded by a project (BAP TF.12.16) from the University of Gaziantep.</i> <h3>Disclosure of Interest</h3> None Declared
Abstract 3485: Insulin-like growth factor binding protein-4 (IGFBP-4) differentially inhibits growth factor induced angiogenesis in vivo
Authors: Liangru W. Contois, Jennifer M. Caron, Eric Tweedie, Leonard Liebes, Robert Friesel, Calvin Vary, Peter C. Brooks
Journal: Cancer Research (2011)

Abstract Angiogenesis contributes to the development and progression of malignant tumors. An expanding body of evidence also suggests that the response of both vascular and tumor cells to growth factor stimulation depends in part on cellular communication with the extracellular matrix (ECM), and studies have documented important roles for the integrin family of ECM receptors in modulating growth factor signaling. Therefore, uncovering molecular mechanisms by which integrin-mediated cellular communication with the ECM modulate the specificity of growth factor signaling during pathological angiogenesis may provide unique insight into malignant tumor progression. Here we provide evidence that disruption of αvβ3-dependent interaction with the ECM enhance expression of Insulin-like growth factor binding protein-4 (IGFBP-4), a well-known regulator of IGF-1 signaling. Interestingly, IGFBP-4 significantly (P&amp;lt;0.05) inhibited IGF-1 and bFGF-induced angiogenesis by greater than 50%. In contrast, IGFBP-4 alone failed to inhibit VEGF-induced angiogenesis in chick CAM. Levels of phosphorylated p38 MAP kinase were elevated in chick CAM tissues treated with VEGF as compared to those in tissues stimulated with either IGF-1 or bFGF. Surprisingly, while the p38 MAP kinase inhibitor SB 202190 alone had little effect on VEGF-induced angiogenesis, a combination of IGFBP-4 and the p38 MAP kinase inhibitor significantly (P&amp;lt;0.05) inhibited VEGF-induced angiogenesis. These novel findings are consistent with a role for elevated levels of activated p38 MAP kinase in modulating the anti-angiogenic activity of IGFBP-4 in vivo. Taken together, our experimental findings provide additional molecular insight into how integrin-mediated interactions with the local ECM microenvironment may modulate the responses of cells to distinct growth factor signaling pathways during angiogenesis. 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 3485. doi:10.1158/1538-7445.AM2011-3485
DECLINE IN MITRAL ANNULAR PLANE SYSTOLIC EXCURSION IN ASYMPTOMATIC PATIENTS WITH AORTIC VALVE STENOSIS AND PRESERVED SYSTOLIC FUNCTION PREDICTS THE CLINICAL NEED FOR AORTIC VALVE INTERVENTION
Authors: Andrew Locke, Jason Matos, Randal Goldberg, Joshua E. Kiss, Kenneth Mukamal, Warren Manning
Journal: Journal of the American College of Cardiology (2016)
Abstract LB-269: A new role for the gain-of-function activity of p53 in breast cancer
Authors: Yves St-Pierre
Journal: Cancer Research (2012)

Abstract Using tissue microarrays constructed from samples obtained from normal breast tissues and breast carcinomas, we previously found that galectin-7 is specifically expressed in myoepithelial cells but not luminal cells. We also found that abnormally high levels of galectin-7 were restricted to basal-like breast cancers, a heterogeneous group of cancers with a poor prognosis. These results were consistent with the genomic profiling data previously reported by the group of Charles Perou who recently provided a molecular portrait of human breast tumors. Their data revealed that while galectin-7 transcripts were expressed at low levels in normal breast tissues and mammary epithelial cell lines, they were highly expressed in estrogen receptor (ER)-negative breast cancer. Our data were also consistent with microarray studies by Jones and colleagues who identified galectin-7 as a myoepithelial-specific genes. In fact, galectin-7 ranked first on a list of 42 most predictive genes that distinguish luminal and myoepithelial cells. This expression of galectin-7 is not only important to study in terms of biomarkers of aggressive forms of breast cancer, but also because increased galectin-7 in breast cancer cells is known to increase their metastatic behavior. However, the expression of galectin-7 in aggressive forms of breast cancer is somewhat paradoxical if not surprising because galectin-7 has been considered an apoptosis regulator under the control of p53. In a previous report, Galectin-7 (also called p53-induced gene 1) was found to be one of the 14 transcripts that were induced by wild-type p53 in colon cancer cells. Here, we have examined this apparent contradiction by investigating the molecular mechanisms controlling galectin-7 expression in human breast cancer cells. We found that galectin-7 expression in human breast cancer cells is dictated by a gain-of-function activity of mutant p53. This conclusion is based on the following: 1) expression of galectin-7 in cancer cell lines correlated with constitutively high levels of NF-κB activity; 2) transfection of NF-κB subunits or treatment of cells with TNFα, a well-known inducer of NF-κB, increased endogenous level of galectin-7; 3) inhibitors of NF-κB reduced constitutive galectin-7 expression; 4) transfection of a transcriptionally inactive form of p53 (R175H) into a p53-null human breast cancer cell line induced galectin-7 via increased NF-kB activity. These findings identify galectin-7 as a novel player through which mutp53 exerts its gain-of-function activity in breast cancer cells. 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 LB-269. doi:1538-7445.AM2012-LB-269
P160 Treating TB patients with no entitlement to social support--welcome to the social jungle
Authors: S. Hemming, P. Windish, J. Hall, A. Story, M. Lipman
Journal: Thorax (2010)

<h3>Background</h3> In the UK, TB medication is free but access to additional resources necessary for treatment completion is conditional. Patients with no recourse to public funds (NRPF), including undocumented and some European Economic Area migrants, have no rights to benefits, public housing or social care. The International Union Against Tuberculosis and Lung Disease (IUATLD) recommends that undocumented migrants with tuberculosis (TB) should receive free treatment and not be deported until completion of treatment. We used case reviews to explore how this guidance translates into current practice in London. <h3>Methods</h3> We reviewed clinical, social circumstances and treatment outcomes for 32 NRPF patients with active TB referred from September 2007 to June 2010 to Find and Treat, a pan-London multi-disciplinary project developed to strengthen TB control in hard-to-reach groups. <h3>Results</h3> The case reviews demonstrated that, while TB medication is free, lack of access to public funds severely compromises treatment access, completion and cure. Patients are unable to pay for transport to attend clinic appointments, buy food or access accommodation. Many (7/32) in fact were sleeping rough. More than a third (10/32) had resistant forms of TB, including 3 to a single drug (Isoniazid) and 7 with Multi Drug resistance (MDR). Despite close working relationships with Border Control Agencies, threat of deportation is a reality. Nine patients (28%) were lost to follow-up care, of which almost half (4/9) have never been found. Consequences included unsupervised medication, street homelessness, hospital admission (including for malnutrition) and treatment interruption and default. <h3>Conclusion</h3> Though ensuring access to free treatment, current guidance does not address the wider determinants of health in tuberculosis. This results in severe inequity of care, and poor treatment outcomes with potentially serious public health implications. Political commitment to provide for basic social needs as well as free medication for all patients is required to effectively control TB.
604 THE INFLUENCE OF SPLENECTOMY ON HEMODYNAMIC AND HEMATOLOGICAL ABNORMALITIES IN CIRRHOTIC AND NON-CIRRHOTIC PORTAL HYPERTENSIVE RATS
Authors: P. Schwabl, B.A. Payer, T.L. Schubert, F. Riedl, M. Wagner, L. Garnys, A.I. Schiefer, T. Reiberger, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2013)
FRI0398 Disease Specific Quality of Life in Patients with Lupus Nephritis
Authors: M. Jolly, S. Toloza, A. Bertoli, I. Blazevic, L. Vila, I. Moldovan, K. Torralba, A. Kaya, B. Goker, M. Tezcan, S. Haznedaroglu, J. Bourre-Tessier, S. Navarra, D. Wallace, M. Weisman, A. Clarke, G. Alarcon, C.C. Mok
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Little is known about patient reported outcomes (PRO) in lupus nephritis (LN), and no studies using a disease targeted PRO tool have been undertaken thus far. <h3>Objectives</h3> To describe quality of life (QOL) among patients with LN using a valid and reliable disease targeted PRO measure (LupusPRO). <h3>Methods</h3> Cross sectional data obtained from patients with systemic lupus erythematosus (SLE) during psychometric evaluation studies of LupusPRO from various countries were compared between those: 1) with and without LN and 2) with active and inactive-LN." Data compared included demographics, disease characteristics, and LupusPRO constructs. Presence of LN was present if listed among the ACR classification criteria (ACR-LN), while presence of active LN was based on presence of urinary casts, hematuria, proteinuria or pyuria in the disease activity assessment (SELENA-SLEDAI) performed at the time of the study visit. LupusPRO has Health related QOL (HRQOL) and non-HRQOL constructs. HRQOL domains include lupus symptoms, cognition, medication, procreation, physical health, emotional health, pain-vitality and body image. Non-HRQOL domains include desires-goals, social support, coping and satisfaction with care. Non-parametric tests were used to make comparisons, and p values ≤0.05 were considered significant. <h3>Results</h3> There were 1,259 SLE patients; ninety-four percent were women and their mean (SD) age was 41.7 (13.5) yrs. Five-hundred and thirty-nine had ACR-LN. These patients were younger, had greater disease activity (PGA, Total SELENA-SLEDAI) and damage (SLICC/ACR) than those without LN. Summary HRQOL and non-HRQOL scores were similar in both groups; however, those with ACR-LN had significantly worse scores on medications and procreation domains, while those without ACR-LN had worse scores on Pain-Vitality domains. 129/540 ACR-LN patients had active LN. Patients with active LN were younger, had significantly greater disease activity (PGA, Total SELENA-SLEDAI), worse HRQOL and non-HRQOL than patients with inactive LN. Specific domains scores adversely affected among active LN patients were lupus symptoms, medications, procreation, emotional health, body image and desires-goals. Satisfaction with care was significantly higher among patients with active LN as compared to inactive LN patients. <h3>Conclusions</h3> LN adversely affects several specific QOL domains and physicians need to be aware of these concerns <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3775
Keith Hodgkin David Lintott Philippa Mary Ludlam Michael Patrick Quinlan Roy Kenneth Rowley
Authors: P. Hodgkin, B. Bury, U. Lutwyche, A. While, S. Rowley
Journal: BMJ (1999)

Former general practitioner Teesside (b Banbury 1918; q Oxford 1943), died from coronary heart disease on 2 June 1999.Keith observed his patients and their symptoms all his life and became a meticulous record keeper.The result was Towards Earlier
Neuroendocrine-Immune Interactions
Authors: Franklin H. Epstein, Seymour Reichlin
Journal: New England Journal of Medicine (1993)

The long-held view that homeostatic mechanisms are integrated by the nervous and endocrine systems has recently been expanded by information that these systems interact with the immune system. Immune responses alter neural and endocrine function, and in turn, neural and endocrine activity modifies immunologic function1. Many regulatory peptides and their receptors previously thought to be limited to the brain or the immune system are now known to be expressed by both. Findings that link immune and neuroendocrine function provide explanations for the response of the pituitary and adrenal glands to infection and inflammation and the alterations in pituitary-thyroid and . . .
FRI0090 Radiographic progression in patients with early rheumatoid arthritis treated with etanercept: results from the prize study
Authors: P. Emery, A. Szumski, H. Jones
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The window of opportunity for optimal outcomes in rheumatoid arthritis (RA) treatment is hypothesised to be very early in the disease.<sup>[1]</sup> At the time of symptom onset, radiographic progression may be rapid and early treatment to slow or prevent irreversible damage is essential. TNF inhibitors have been shown to slow or halt radiographic progression. <h3>Objectives</h3> This posthoc analysis examines responses to 52 weeks (wks) of etanercept (ETN)/methotrexate (MTX) based on modified Total Sharp Scores (mTSS) at baseline (BL) in patients (pts) with early RA (symptom onset ≤12 months) in the PRIZE study (NCT00913458). <h3>Methods</h3> Pts received ETN50/MTX for 52 wks. In this posthoc analysis, pts were stratified by mTSS at BL (≤3 vs. &gt;3<sup>[2]</sup>) and by radiographic progression at wk 52 (ΔmTSS ≤0 vs. &gt;0) and were then examined for efficacy, looking at DAS28ESR, CDAI, SDAI, ACR 20/50/70and ΔmTSS. LOCF imputation, chi-square and CMH tests were used; mTSS was extrapolated to wk 52. <h3>Results</h3> At BL, similar subpopulations (N=269) had mTSS &gt;3 (n=141, mean mTSS=13.8) and ≤3 (n=128, mean mTSS=1.5); pts with mTSS&gt;3 had higher age, serum CRP, symptom duration and lower percent of females (mean 54 yrs, 18 mg/L, 6.9 mo, 59%) than those with mTSS ≤3 (45 yrs, 14 mg/L, 6.1 mo, 77%, P&lt;0.05). At week 52, pts with mTSS &gt;3 at BL achieved better improvement than those with mTSS ≤3 in DAS28ESR, CDAI, CRP and ESR (P&lt;0.05 for all). For endpoints at week 52, nominally more pts with BL mTSS≤3 x wk 52 ΔmTSS&gt;0 and pts with BL mTSS&gt;3 x wk 52 ΔmTSS≤0 achieved ACR50/70 and CDAI/SDAI remission than other pts (table). <h3>Conclusions</h3> Regardless of the amount of joint damage at baseline, disease states improved after 52 weeks for ΔmTSS for all clinical outcomes examined. A large percent of patients achieved remission which may have impacted relationships between progression and outcomes. More research is needed on the predictive value of mTSS for outcomes of RA treatment. <h3>References</h3> Quinn, M.A. and P. Emery, Clin Exp Rheumatol, 2003. <b>21</b>(5 Suppl 31): p. S154–7. 2. Bruynesteyn, K., et al., Arthritis Rheum, 2002. <b>46</b>(4): p. 913-20. <h3>Acknowledgements</h3> The PRIZE study (ClinicalTrials.gov, NCT00913458) was sponsored by Pfizer Inc. The authors would like to thank Thomas Jones, Andrew S. Koenig and Eustratios Bananis of Pfizer Inc for thoughtful reviews of this abstract. Medical writing support was provided by Patricia McChesney of UBC Scientific Solutions and funded by Pfizer Inc. <h3>Disclosure of Interest</h3> P. Emery Consultant for: Abbott, Bristol-Myers Squibb, Merck, Novartis, Pfizer Inc, Roche-Chugai, UCB Pharma Ltd, A. Szumski Employee of: Pfizer Inc, H. Jones Shareholder of: Pfizer Inc, Employee of: Pfizer Inc
Abstract 1621: Short-time exposure to high concentrations of sunitinib causes tumor cell death.
Authors: Maria Rovithi, Dennis Poel, Jens Voortman, Mariette Labots, Henk Dekker, Kristy J. Gotink, Henk J. Broxterman, Henk M.W. Verheul
Journal: Cancer Research (2013)

Abstract Background: Sunitinib, although initially developed as an antiangiogenic agent, has been shown to exert direct anti-tumor effects. Previously we demonstrated that sunitinib inhibits proliferation of various tumor cell lines in a dose-dependent manner. We here studied whether short exposure to high peak concentrations of sunitinib would induce tumor cell death. Methods: 786-O renal cancer cells were incubated with increasing concentrations of sunitinib (5, 10 and 20 μM) for various time intervals (1 hour, 3, 6, 9, 24, 48, 72 hours). At prespecified time points, sunitinib was removed and cells were subsequently allowed to grow in drug-free culture medium. Viability of these cells one week after short time sunitinib exposure and sensitivity of recovered cells after repetitive treatment with high sunitinib concentrations were determined by MTT assays. Flow cytometry with Propidium Iodide staining was employed to determine apoptosis. Results: Short-time exposure to high concentrations of sunitinib significantly induced cell death. Exposure to 20 μM of sunitinib for 9 hours provoked cell death in a manner identical to the prolonged exposure of 24, 48 or 72 hours. Flow cytometry confirmed the significant increase in cell death (60%) after 9-hour treatment with 20 μM sunitinib, compared to the untreated control (2%). Tumor cells that were repetitively treated with high concentrations of sunitinib retain their sensitivity to the drug identical to its parental cell line. Analysis of the key signaling pathways involved in sunitinib-induced cell death is ongoing. Conclusion: We here report that repetitive short-time exposure to high concentration sunitinib causes cell death without inducing resistance. Interestingly, single-dose sunitinib up to 300 mg was previously reported to be well tolerated by patients. Based on these findings, administration of high dose intermittent sunitinib may result in cytotoxic antitumor activity irrespective of angiogenesis inhibition. A phase I trial to test this hypothesis in patients with cancer will start shortly. Citation Format: Maria Rovithi, Dennis Poel, Jens Voortman, Mariette Labots, Henk Dekker, Kristy J. Gotink, Henk J. Broxterman, Henk M.W. Verheul. Short-time exposure to high concentrations of sunitinib causes tumor cell death. [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 1621. doi:10.1158/1538-7445.AM2013-1621
TCT-503 Prevalence of CYP2C19 Variants and Associated Stent Thrombosis in Patients Undergoing Percutaneous Coronary Intervention
Authors: Janarthanan Sathananthan, Seif El-Jack, Ali Khan, Guy Armstrong, Jonathan Christiansen, Tony Scott, Mehran Zareian, Kevin Smith, Lifeng Zhou, Patrick Gladding
Journal: Journal of the American College of Cardiology (2014)
MITRAL VALVE INDEX: A SIMPLE AND ROBUST PARAMETER FOR DETECTING PROSTHETIC MITRAL VALVE REGURGITATION
Authors: Sushil Allen Luis, Lori Blauwet, Ramila Mehta, Himabindu Samardhi, Cathy West, Chris Luis, Gregory Scalia, Fletcher Miller, Darryl Burstow
Journal: Journal of the American College of Cardiology (2015)
Voters and the Affordable Care Act in the 2014 Election
Authors: Robert J. Blendon, John M. Benson
Journal: New England Journal of Medicine (2014)

In this analysis of data from 27 public opinion polls, the authors examine the role of the Affordable Care Act in the 2014 congressional elections. The outcome of the elections is likely to influence implementation of the ACA and future U.S. health care policy.
Efficacy of Conventional Pituitary Irradiation in Acromegaly
Authors: Jesse Roth, Phillip Gorden, Kirkland Brace
Journal: New England Journal of Medicine (1970)

External irradiation of the pituitary gland with 4000 Ft from a conventional supervoltage source reduced plasma growth hormone in 19 of 20 patients with acromegaly. By one to two years after irradiation, the mean fall in plasma hormone concentration for the entire group was 51 per cent (range, 0 to 88 per cent). In seven patients who were studied again at two and a half to four years, the mean decrease was 76 per cent (60 to 89 per cent). Of seven untreated but otherwise comparable patients, one had a slight reduction, one had no change, and five had rises in plasma hormone concentrations over similar periods of observation. The only complication of irradiation was hair loss at the temples. The falls in plasma growth hormone and the wide variation in benefit among individual patients that we observed with conventional external irradiation are indistinguishable from results reported by others for proton-beam irradiation, implants of radioactive yttrium, cryohypophysectomy and surgical hypophysectomy.