tbuckley/cabot-search huggingface dataset:
Serial Occurrence of Two Types of Postpartum Thyroid Disorders
Authors: Takashi Misaki, Shinichi Miyamoto, Kanji Kasagi, Toru Mori, Junji Konishi
Journal: Clinical Nuclear Medicine (1996)

A 32-year-old woman with a history of Graves' disease had an episode of thyrotoxicosis 2.5 months after her first childbirth. Because of low thyroidal uptake of Tc-99m pertechnetate, a diagnosis of postpartum painless thyroiditis was made and the patient was observed without medication. After the normalization of serum levels of thyroid hormones, a second wave of thyrotoxic symptoms emerged. This time, the Tc-99m uptake was slightly elevated and the patient was diagnosed to have a relapse of Graves' disease. This case underscores the previously reported notion that thyroidal uptake was indispensable to distinguish these two causes of postpartum thyrotoxicosis.
Abstract LB-47: The Prostate Net: We Inform To Fight
Authors: Janet Arias
Journal: Cancer Research (2012)

Abstract The Prostate Net (TPN) is a non-profit patient education and advocacy organization dedicated to serving Prostate Cancer patients and their caregivers. Using the experience gained as a marketing professional and as a 16-year Prostate cancer survivor, TPN founder and president Virgil Simons has built an international organization that uses websites, 800 numbers, email and personal team counselors, newsletters and public forums to address disease risk awareness and early intervention. TPN's core objectives are to (1) Educate consumers most at-risk for a diagnosis of prostate cancer; (2) Inform the community on co-morbid diseases and conditions of negative impact; (3) Motivate consumers to make informed choices about healthcare and lifestyle management; (4) Lay the foundation for on-going healthcare information dissemination and interaction between the community and medical centers; and (5) Create an interactive network to maximize broad scale, mass communications of actionable health messages. 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-47. doi:1538-7445.AM2012-LB-47
Abstract B40: Histone H3 methylation couples DNA damage detection to activation of the Tip60 tumor suppressor
Authors: Yingli Sun, Brendan Price
Journal: Cancer Research (2009)

Abstract Cancer is a heterogeneous disease which arises primarily from the accumulation of mutations and deletions in the cells DNA. However, recent work has implicated both DNA methylation and histone modifications in the etiology and progression of cancer. For example, abnormal patterns of histone methylation have been identified in breast cancer, raising the possibility that altered patterns of histone methylation can be exploited both as a biomarker to monitor disease status and as a novel therapeutic target. Here, we report on a novel role for histone methylation in regulating the ability of the Tip60 acetyltransferase to repair DNA double strand breaks (DSBs). Tip60 is a haplo-insufficient tumor suppressor, and loss of heterozygosity at the Tip60 locus and reduced levels of nuclear Tip60 have been detected in both breast and prostate cancer. Tip60 is an acetyltransferase, and can acetylate several DNA repair proteins implicated in breast cancer, including myc, p53 and ATM. Previously, we demonstrated that Tip60 acetylates and activates the ATM protein, a key component of the cells DSB repair mechanism. Here, we demonstrate that methylation of histones creates docking sites for the recruitment of the Tip60 DNA repair complex to sites of DNA damage. Further, interaction between Tip60 and methylated histones serves to specifically activate Tip60'fs acetyltransferase activity at DSBs. Reduction in histone methylation levels compromises Tip60 activation, leading to reduced DNA repair and increased genomic instability. These results indicate that the level and distribution of specific histone methylation marks across the chromatin is a critical determinant of cells ability to repair and survive DNA damage. Thus histone methylation may regulate the genomic stability of cells and their intrinsic sensitivity to agents, including radio- and chemo-therapy, which directly damage DNA. Altered histone methylation associated with breast cancer may therefore contribute to both genomic instability and to resistance to therapy. Finally, since histone methylation is reversible, the enzymes controlling histone methylation represent an exciting new target for therapy in breast cancer. Citation Information: Cancer Res 2009;69(23 Suppl):B40.
Abstract LB-25: Activation of AMPK by ATM in reponse to AICAR and metformin
Authors: Da-Qing Yang, Margot P. Cleary
Journal: Cancer Research (2012)

Abstract AMPK is an AMP-activated protein kinase that plays a key role in regulating cellular energy homeostasis. Metabolic stress, such as heat shock and glucose starvation, causes energy deficiency in the cell and leads to elevated levels of intracellular AMP. This results in the phosphorylation and activation of AMPK. LKB1, a tumor suppressor, has been known as an upstream kinase of AMPK. We found that in response to treatment with 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR), a LKB1-null cancer cell line, HeLa, still exhibited AMPK phosphorylation. This indicates the existence of an LKB1-independent AMPK protein kinase. ATM is a protein kinase that is deficient in the disease ataxia telangiectasia (A-T). We measured the activation of AMPK by AICAR in the normal mouse embryo fibroblast (MEF) cell line, A29, and the MEF cell line lacking the ATM protein, A38. In A38 cells, the level of AICAR-induced AMPK phosphorylation was dramatically lower than that found in A29 cells. Furthermore, phosphorylation of AMPK in HeLa and A29 cells was inhibited by an ATM specific inhibitor, KU-55933. Our results demonstrate that AICAR treatment could lead to phosphorylation of AMPK in an ATM-dependent and LKB1-independent manner. Similar to the results of AICAR treatment, our work also revealed that the metformin-induced phosphorylation of AMPK in A38 cells is significantly lower than that in A29 cells. We also examined the effect of ATM on AMPK in rat hepatoma cell line H4IIE. Inhibition of ATM by KU-55933 dramatically reduced the phosphorylation of AMPK in response to metformin in this cell line. Thus, ATM may act as a potential AMPK kinase in response to both AICAR and metformin treatment. Metformin is the most commonly prescribed pharmaceutical drug for type 2 diabetes (T2D). In addition, patients with T2D or obesity/insulin resistance who take metformin have reduced rates of cancer occurrence, including breast cancer. However, the mechanism underlying metformin's effect on cancer prevention and/or treatment is unclear (Nature, New &amp; views, Feb. 2011; Science, News Focus, Jan. 2012). While ATM acts as a sensor of DNA damage by controlling cell cycle progression, it also has glucose regulatory function. Our results put ATM as a novel player in the AMPK signaling pathway in response to metformin. These findings provide new insights into the mechanisms by which metformin functions as a preventive and/or therapeutic agent for cancer. 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-25. doi:1538-7445.AM2012-LB-25
PWE-190 Endoscopic mucosal resection of large colorectal polyps: outcomes from a regional bowel cancer screening centre
Authors: R Kalla, S M Ali, C Grimley, J Salaman, R Hart, C Shorrock, L Newton, J Statham, M T Hendrickse
Journal: Gut (2012)

<h3>Introduction</h3> Endoscopic mucosal resection (EMR) of colorectal polyps has been reported to be a safe and effective technique within the UK. Most series have however included smaller polyps (1 cms or less) and there is paucity of data on EMRs limited to large polyps. We report the outcomes on a series with large polyps (&gt;2 cms) from a bowel cancer screening centre in the UK. <h3>Methods</h3> A total of 5190 polypectomies were performed within the region from January 2008 to December 2011 on the Bowel Screening Programme. Data were collected from three hospitals on all large polyp EMR greater than 2 cm in size. Data were analysed using the SPSS V.20. <h3>Results</h3> A total of 61 patients with polyps 2cm or greater were identified. The mean age was 69 years, 75% (n=46) of which were male. The mean size of the polyps resected was 35 mm (range 20–60 mm). The majority of the polyps were sessile (n=40) and located in the left colon (n=43). Tattooing was performed in 46% (n=28) and Argon-beam photocoagulation (APC) therapy was applied in 41% of cases (n=25). In 97%, the resections were complete (n=59). Histopathology results were obtainable in 57 patients of whom 12% (n=7/57) showed high grade dysplasia and 5% (n=3/57) were confirmed as adenocarcinoma. The overall major complication rate was 3% (n=2). Both complications were bleeding post-EMR. Surveillance data were available for 43 patients up-to 12 months post EMR. Six recurrences (10%) were seen at the EMR site at 3 months, five of these in left colon. On reviewing their initial EMR, the polyps had a median size of 25±6 mm; 50% (n=3/6) had APC therapy and 5/6 the excision was endoscopically complete on initial EMR. Histology confirmed low grade dysplasia (LGD) in all cases. Recurrence was endoscopically treated successfully in all cases. Recurrence rate was not influenced by the size or site of the polyp or APC therapy. Sessile polyp EMR were more likely to show recurrence (n=5/6). At 12 months, eight patients had recurrence. Six of these patients had endoscopically complete excision on initial EMR. On reviewing their initial EMR, the polyps had a median size of 35±5 mm; 50% had APC therapy. Recurrence was treated successfully in all cases. <h3>Conclusion</h3> Endoscopic mucosal resection for large colorectal polyps is safe with relatively low complication rates compared to laproscopic surgery. Recurrence rate is low at 3 months but can still occur upto 12 months in lesions felt to be completely excised. <h3>Competing interests</h3> None declared.
AB0566 Evolution of Xerostomia, Xerophthalmia and Salivary Test of Caries Risk of Primary SjÖgren's Syndrome During Pregnancy: Table 1
Authors: E. Trujillo, E. Padron, L. Exposito, M. Garcia, H. Sanchez, M.M. Trujillo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Healthy life expectancy (HLE) is a population health measure that combines mortality and morbidity, which can be calculated using different methods. In this study, we aimed to assess the correlation, reliability and (dis)agreement between two estimates monitored in the European Union (EU), that is, the European Commission9s HLE based on self-perceived health (SPH-HLE) and the Institute for Health Metrics and Evaluation9s HLE based on disability weight (DW-HLE), by sex, and comparing these results with LE and proportion of life spent in good health (%GH). <h3>Methods</h3> We performed a retrospective study in the EU28 countries, between 2010 and 2017. The HLE methods differ in definition, measurement and valuation of health states. While SPH-HLE relies directly on one question, DW-HLE relies on epidemiological data adjusted for DW. Spearman’s r, intraclass correlation coefficient, information-based measure of disagreement and Bland-Altman plots were used to assess reliability, correlation and disagreement in HLE resulting from both methods and in LE or %GH measured by both institutions. <h3>Results</h3> Correlation and reliability between SPH-HLE and DW-HLE were good (better for males), with low disagreement, and were even better for LE between both institutions. The HLE Bland-Altman plots suggest a variability range of approximately 6 years for both sexes, higher for females. There was also an increasing HLE difference between methods with higher average HLE for both sexes. <h3>Conclusion</h3> We showed wide variations between both methods with a clear and different high impact on female and male HLE, showing a tendency for countries with higher health expectancies to yield larger gaps between SPH-HLE and DW-HLE.
AB0638 Corticosteroid Use and Arterial Hypertension Are Independent Risk Factors Associated with Low Glomerular Filtration Rate in Systemic Sclerosis
Authors: P. Ostojic, N. Stojanovski, N. Damjanov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Apart from scleroderma renal crisis, which is a rare but life-threatening condition in systemic sclerosis (SSc), many patients demonstrate less severe renal complications, probably associated with reduced renal blood flow and the consequent reduction in glomerular filtration rate (GFR). <h3>Objectives</h3> To identify risk factors associated with reduced GFR in patients with SSc. <h3>Methods</h3> 73 consecutive patients with SSc (67 women and 6 men), mean age 56.2 years, mean disease duration 6.7 years, were included in this study. Fifty (68.5%) of patients had limited SSc, and 23 (31.5%) had diffuse form of the disease. ACA were positive in 27 (37%) and ATA in 34 (46.6%) of patients. GFR was assessed by calculating creatinine clearance (CCr) in all patients. CCr values ≥90ml/min were considered normal. There are four stages of renal insufficiency depending on the calculated CCr value: <i>mild</i> (60-89ml/min), <i>moderate</i> (40-59ml/min), <i>severe</i> (15-39ml/min) and <i>terminal (end-stage)</i><i>renal failure</i> (less then 15ml/min). We assessed the prevalence and severity of renal insufficiency in our patients with SSc, and estimated the relationship with age, disease duration, earlier diagnosed arterial hypertension and the use of medications which may have impact on renal function (cytostatics, NSAIDs, corticosteroids, ACE inhibitors, diuretics and calcium channel blockers). The univariate General Linear Model (GLM), ANOVA, Mann-Whitney and Student9s T-test from SPSS 14.0 software were used for statistical analyses. <h3>Results</h3> Decreased GFR was noticed in 56/73 (76.7%) of patients with SSc. Mild renal insufficiency was present in 28/73 (38.4%), moderate in 21/73 (28.8%), severe in 5/43 (6.8%) and terminal in 2/73 (2.7%) of patients. Age, disease duration, cytostatics or NSAIDs were found not to be risk factors associated with low GFR. On the other hand, we have noticed a statistically significant association between corticosteroid use and reduced GFR (F=11.89, p=0.001), as well as previously diagnosed arterial hypertension and reduced GFR (F=4.77, p=0.03). Moreover, mean GFR was significantly lower (F=4.88, p=0.008) in SSc patients and arterial hypertension treated with ACE-inhibitors (41.7ml/min) or diuretics (53.5ml/min), than in patients treated with calcium channel blockers (90.4ml/min). <h3>Conclusions</h3> Corticosteroid use and arterial hypertension are independent risk factors associated with reduced GFR in SSc. Compared to calcium channel blockers, ACE-inhibitors and diuretics, used to treat arterial hypertension in our patients, are associated with lower GFR. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3428
P478Ablation of CD8+ dendritic cell mediated cross presentation does not impact atherosclerosis in LDLR deficient mice
Authors: B R J Legein, E Janssen, E Lutgens, E Biessen, L Temmerman
Journal: Cardiovascular Research (2014)

Background: Dendritic cells (DCs) are professional antigen presenting cells, essential in linking innate to adaptive immunity. In particular CD8+ DCs can acquire exogenous antigens for direct presentation on MHC I molecules to CD8+ T cells, a process known as cross presentation. The importance of this process is well established in the field of tumor immunology, where CD8+ DCs take up necrotic material and prime CD8+ T cells to kill tumor cells. Although all important players for cross presentation are present in advanced atherosclerosis, little is known regarding its contribution to the pathophysiology of this disease. We therefore sought to investigate this by a loss-of-function approach using batf3-/- chimeric mice, which specifically lack CD8+DCs.

Methods: LDLR-/- mice were transplanted with either batf3-/- or wt bone marrow and after recovery, put on a western type diet (WTD) for 10 weeks. Histology was performed on aortic arch and root sections, while blood and lymphoid organs were analyzed by flow cytometry. Cross presentation capacity was investigated using the CD8+ OT-I T cell- actmOVA model.

Results: Hematopoietic batf3 deficiency sharply decreased CD8+DC numbers in spleen and mesenteric LNs (>80% compared to WT transplanted controls; P<0.001). Concordant with this reduction, batf3-/- transplanted mice had a 75% reduction in OT-I cross-priming capacity in vivo, establishing the significance of this subset for OVA cross-presentation, even in hyperlipidemia. Furthermore, batf3-/- transplanted mice did not show lower CD8+ T cell numbers, nor did batf3 deficiency have an effect on CD4+ T cell numbers or on other leukocyte subsets. Surprisingly, despite the dampened cross presentation capacity, batf3-/- mice had unchanged atherosclerosis burden and plaque progression in the aortic arch and root. Likewise, plaque T cell infiltration or cell death did not differ between batf3-/- and WT transplanted mice, as assessed by CD3 and caspase 3 staining, respectively.

Conclusion: While CD8+DC loss during atherosclerosis development profoundly reduces cross priming ability, it does not notably affect activation status or numbers of other leukocyte populations nor does it influence lesion development in WTD fed LDLR-/- mice.

Taken together, our data clearly demonstrate that CD8+ DCs do not significantly contribute to atherosclerotic plaque formation and stability.
Abstract 1906: Differential downstream effects of nicotinamide adenine dinucleotide (NAD) salvage pathway-inhibition in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM).
Authors: Iris Gehrke, Armando Poeppl, James Johnston, Spencer B. Gibson, Versha Banerji
Journal: Cancer Research (2013)

Abstract Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) represent the two most common hematologic malignancies in western countries. Up to date both diseases are mainly treated palliatively rather than curatively which reinforces the need for new treatment options. Targeting metabolism-associated pathways is a novel route for treatment of hematologic malignancies. Nicotinamide adenine dinucleotide (NAD) is not only a central molecule for metabolic processes such as ATP-generation, but is also involved in several other cancer-relevant events. The NAD-dependent enzyme Sirtuin 1 (Sirt1) has been described to function as an oncogene. Further, the rate-limiting enzyme for NAD-generation via salvage-pathways nicotinamide phosphoribosyltransferase (NAMPT) is upregulated in several cancers, making it an attractive metabolism-associated drug target. We used the NAMPT-inhibitor FK866 to treat the MM-cell line IM9 and the CLL-like cell lines JVM3 and Mec2 as well as primary CLL-cells. Cellular energy status was assessed by means of ATP content and functioned as a measure of viability. Sirt1 levels were assessed by immunoblotting. The MM-cell line IM9 was highly sensitive to FK866 with regard to ATP-reduction (50% reduction at 51.7nM). Also the tested CLL-like cell lines JVM3 and Mec2 were sensitive to FK866 with 50% reduction of ATP content at 76.6nM and 51.1nM, respectively. Primary CLL cells showed very heterogenous response. Some samples were highly sensitive with 50% reduction of ATP-content at 21.6nM, while others were completely resistant. We could not detect any correlation to available clinical data such as ZAP70 status or white blood cell counts. All three cell lines were positive for Sirt1. While the two CLL-like cell lines Mec2 and JVM3 showed a concentration-dependent downregulation of Sirt1 upon FK866 treatment for 72h, Sirt1 levels remained stable in the MM-cell line IM9. Primary CLL-cells showed various baseline levels of Sirt1 and a concentration-dependent downregulation upon FK866 treatment. We conclude that FK866 activity in CLL-like cell lines involves downregulation of the NAD-dependent oncogene Sirt1, while FK866 activity in the MM-cell line IM9 is Sirt1-independent. In primary CLL-cells Sirt1 baseline levels may predict responsiveness to FK866 treatment. Citation Format: Iris Gehrke, Armando Poeppl, James Johnston, Spencer B. Gibson, Versha Banerji. Differential downstream effects of nicotinamide adenine dinucleotide (NAD) salvage pathway-inhibition in chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). [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 1906. doi:10.1158/1538-7445.AM2013-1906
AB0101 Effect of aerobic exercise in experimental model of arthritis
Authors: P. V. G. Alabarse, P. R. Viacava, L. L. Xavier, V. O. N. Teixeira, L. I. Filippin, R. M. Xavier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease of unknown etiology, affecting not only the joints but also other tissues such as skeletal muscle [1]. Muscle loss is a secondary manifestation that impairs the function and quality of life of patients with RA [1]. Physical exercise is associated with reduced morbidity and other beneficial effects inseveral diseases [2, 3]. <h3>Objectives</h3> To evaluate the effect of aerobic exercise on muscle loss of animals with collagen-induced arthritis (CIA). <h3>Methods</h3> CIA was inducedin male mice DBA/1J asdescribed by Brand, 2010 [4]. The animals were divided into two CIA groups: <i>(i)</i> animals with exercise (protocol: walking for 30 min, from 9 to 15 m.min<sup>-1</sup>, three times a week for 4 weeks after the onset of the disease), <i>(ii)</i> animals without exercise. Clinical score and paw swelling were assessed daily during all the experimental period. The weight of the animals and spontaneous exploratory locomotion were evaluated weekly. After death, the myofiber area of the tibialis anterior and gastrocnemius muscles were evaluated as well as ankle joint histopathology. For statistical analysis, t-test were performed and statistical significance was considered for p values p&lt;.05. <h3>Results</h3> No significant difference was observed in clinical parameters of disease activity (clinical score, paw swelling and animal weight) and spontaneous locomotion in the walking group compared with the group without exercise. Although not significant, exercise slightly decreased joint inflammation (1.6 ± 0.17 and 1.9 ± 0.20 arbitrary value, p=.16) and bone erosion (1.3 ± 0.26 and 1.8 ± 0.23 arbitrary value, p=.12), besides that, cartilage erosion were significantly reduced in exercised joint (1.3 ± 0.26 and 1.8 ± 0.23 arbitrary value, p&lt;.05). However, there was significant difference in the myofiber sectional area: exercised CIA showed greater myofiber cross-sectional area compared to the group without exercise (598 ± 58 μm<sup>2</sup> and 481 ± 63 μm<sup>2</sup>, respectively, p&lt;.05), representing a difference of 24%. <h3>Conclusions</h3> This is the first intervention study with forced walk in the experimental model CIA. According to results, aerobic exercise applied from the first clinical signs showed benefit over cartilage erosion and muscle atrophy in an experimental model of arthritis, observed mainly by the reduction of myofiber area, but does not seem to impact in the process of arthritis. <h3>References</h3> McInnes IB, Schett G. <i>New England Journal of Medicine</i> 2011, <b>365</b>(23). Navarro F et al. <i>Cell Biochemistry and Function</i> 2010, <b>28</b>(4):266-273. Nader GA, Lundberg IE. <i>Current Opinion in Rheumatology</i> 2009, <b>21</b>(6):599-603. Brand DD et al. <i>Nature Protocols</i> 2007, <b>2</b>(5):1269-1275. <h3>Disclosure of Interest</h3> None Declared