tbuckley/cabot-search huggingface dataset:
Influence of Age on Secretion of Cholesterol and Synthesis of Bile Acids by the Liver
Authors: Kurt Einarsson, Klas Nilsell, Barbro Leijd, Bo Angelin
Journal: New England Journal of Medicine (1985)

Supersaturation of bile with cholesterol predisposes to the development of cholesterol gallstones. To identify the factors determining cholesterol saturation of bile, we analyzed the lipid composition of stimulated duodenal bile in 60 healthy subjects of various ages (31 men and 29 women) who were not obese and were free of gallstones. A positive correlation between age and cholesterol saturation of bile was found (P<0.001). To analyze the relation between age and cholesterol saturation, we studied the rates of hepatic secretion of biliary lipids and the kinetics of cholic acid and chenodeoxycholic acid in 22 and 18 of the subjects, respectively. Age was positively correlated with the cholesterol secretion rate (r = 0.48) and negatively correlated with bile acid synthesis (r = -0.60) and the size of the cholic acid pool (r = -0.54). We conclude that cholesterol saturation of bile increases with age as a consequence of enhanced hepatic secretion of cholesterol and decreased bile acid synthesis. These findings may explain why age is a risk factor for the development of cholesterol gallstones. (N Engl J Med 1985; 313:277–82.)
P114 Pulmonary Function Progression in Langerhans Cell Histiocytosis: Abstract P114 Table 1
Authors: SR Krivinskas, A Chu, PW Ind
Journal: Thorax (2012)

<h3></h3> Langerhans Cell Histiocytosis (LCH) is a rare, dendritic cell disorder commonly involving the lungs either alone, (PLCH) or as part of multi-system disease (MSLCH). The natural history is variable, ranging from spontaneous resolution to progressive respiratory failure and death. Until recently there were no large follow up series containing lung function data (Tazi A et al, ERJ 2012; 02107–2011). We retrospectively compared pulmonary function over time in patients with PLCH and in MSLCH with lung involvement from our database of 83 adult LCH patients. 46 patients were male; mean age at diagnosis was 34 (range 16–76) years (y). 9/83 patients, 4 male, mean age 32 y, had PLCH. 21/83 13 male, mean age 28y, had MSLCH with lung involvement. All PLCH had smoked with mean 14 pack-y. 7 continued smoking after diagnosis. Initial lung function (n=8) at a mean of 1 (–1 to +3) y post-diagnosis, showed wide variation in spirometric volumes, flows and gas transfer measurements (See table). 1 patient had obstructive, 2 restrictive, 3 mixed patterns, 1 isolated reduction in gas transfer and 2 were normal. 18/21 MSLCH had smoked; mean 12 pack-y. 10 continued smoking after diagnosis. Initial lung function (n=14) at mean 2 (0–12) y post-diagnosis showed slightly less impairment than PLCH but again wide variation. In PLCH (n=7) at mean follow up of 7 (2–10) y, mean changes in lung function were minor but there was variation; 2 patients deteriorated significantly. 4/9 patients received treatment. To date, 1 has died, 5 are in remission and 3 have active disease. In MSLCH (n=12) at mean follow up of 7 (1–16) y, mean changes in lung function were minor apart from 2 patients who showed major reductions. 17/21 patients received treatment. To date 3 have died, 12 are in remission and 6 have active disease. Pulmonary involvement in LCH and impairment of lung function are common in both single and multisystem disease. Changes in lung function over time are very variable with some patients showing marked deterioration and others minor improvement. Lung function determination is important in monitoring all LCH patients with lung involvement.
NI-64 * 3D-PRINTED MRI-BASED CUSTOM BRAIN MOLDS FOR MINIMIZING TISSUE DISTORTION AND PRECISELY SLICING TISSUE FOR CO-REGISTRATION WITH CLINICALLY ACQUIRED MRI IN GLIOMA PATIENTS
Authors: B. Pellatt, N. Mickevicius, E. Cochran, P. LaViolette
Journal: Neuro-Oncology (2014)

INTRODUCTION: Precise co-registration of brain tissue and medical imaging is critical for validation of novel imaging biomarkers meant to detect infiltrative brain cancer. Brain tissue distortion during fixation, and brain slicing in sub-optimal orientation can complicate co-registration. METHODS: Three high-grade glioma patients undergoing brain only autopsies were included in this analysis. A clinically acquired MRI was used to render 3D computer assisted drafting (CAD) models. To generate a fixation cage for preventing tissue distortion, a high-resolution 3D-T1-weighted MRI scan was used to generate a solidified mesh with approximately 500 holes to allow formalin exposure. The left and right hemispheric meshes were then 3D printed in plastic using a MakerBot Replicator2X. The brains were fixed in formalin for approximately 14 days within the plastic meshes. To generate a slicing mold for one patient, the shell from the 3D-T1-weighted scan was combined with the slice profile of 6.5mm thicker-cut images. A slicing mold was then designed and 3D-printed with slots oriented vertically with the brain lying on its side within the mold. To assess consistency, the thickness of each slice was measured. To assess the co-registration with the patient's clinical MRI, gyri and sulci from each MRI slice were identified and compared to the corresponding tissue slice. RESULTS: The 3D-printed brain cages took approximately 16hrs per hemisphere to print using approximately 1.6lbs of plastic (∼$35/brain). The custom brain-slicing mold took approximately 22hrs to print totaling about 1.2lbs of plastic (∼$26). The average tissue slice thickness was 6.9mm compared to the 6.5mm MRI slices. Of the 188 gyri and sulci identified on in tissue slices 73% co-localized precisely with those seen in corresponding MRI slices. CONCLUSION: 3D printed brain cages and slicing molds provide affordable means for preventing tissue distortion and precisely slicing brain tissue for co-registration with imaging acquired prior to death.
A5.13 Antibody responses to common viruses in patients with rheumatoid arthritis
Authors: N Sherina, H Sigridur, C Bengtsson, L Alfredsson, L Klareskog, K Lundberg
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition where <i>HLA DRB1</i> shared epitope (SE) alleles and cigarette smoking constitute well-established risk factors. Still, current knowledge does not explain the whole risk for developing RA. An attractive hypothesis has been that RA is triggered by an infection, and since the early eighties, when the Epstein Barr virus (EBV) was first linked to RA, a number of studies have investigated the role of viruses in RA aetiology, although with conflicting results. Since most studies have been small, or poorly controlled, or not set in the context of anti-citrullinated protein antibodies (ACPA), SE and smoking, it has been difficult to draw any conclusions. Hence, to further elucidate the role of common viruses in RA aetiology, we have analysed the prevalence of anti-virus antibodies in the well-characterised population-based RA case-control cohort EIRA. <h3>Material and methods</h3> The antibody response to EBV, cytomegalovirus (CMV) and parvovirus B19 was analysed by ELISA in serum from 1000 EIRA RA cases and 700 EIRA controls. Data on ACPA, smoking and SE status was obtained from the EIRA database. Fisher's exact test and Mann-Whitney <i>U</i> test for independent groups were used in the statistical analyses of antibody levels. Unconditional logistic regression analysis was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for the association of anti-virus antibodies with different RA subsets. The additive interaction was evaluated between smoking/SE and virus exposure in ACPA+ RA. <h3>Results</h3> There was a high prevalence of anti-virus antibodies in EIRA, but with no significant differences between RA cases and controls (98.3% vs. 97% for anti-EBV IgG; 75.8% vs. 72.8% for anti-B19 IgG; 72.2% vs. 75.9% for anti-CMV IgG, in RA cases and controls, respectively), and ACPA had no effect on presence/absence of anti-virus antibodies. When comparing anti-virus antibody levels, anti-EBV IgG and anti-B19 IgG levels were significantly lower in ACPA+ RA compared to controls, and there was an interaction between low levels/absence of both anti-EBV and anti-B19 antibodies and SE in the development of ACPA+ RA, while smoking had no effect. <h3>Conclusion</h3> High levels of virus antibodies were not positively associated with RA, irrespective of ACPA, SE or smoking status. If anything there was an inverse association. Hence, our study cannot support a role for these specific viruses in RA aetiology.
Hydrocolonic Ultrasonography in the Detection of Colonic Polyps and Tumors
Authors: David W. Chui, Gretchen Gooding, Kenneth R. McQuaid, Virginia Griswold, James H. Grendell
Journal: New England Journal of Medicine (1994)

Hydrocolonic ultrasonography -- abdominal ultrasonography in conjunction with the retrograde instillation of water into the colon -- has been advocated as an alternative to colonoscopy for detecting colorectal polyps and cancer. We conducted a prospective, blinded trial to evaluate the procedure further.
Abstract 5140: The functional c-Myc dependent polymorphisms of telomerase promoter control <i>hTERT</i> expression and are associated with telomere length
Authors: Son Ji Woong, Yi Young Choi, Jae Yong Park, Hyo-Sung Jeon
Journal: Cancer Research (2012)

Abstract Telomere shorting occurs after repeated cell division and has a key role in cell senescence, differentiation, and immortalization. Thus, telomere maintenance is critical for cancer progression. Telomere length is mainly regulated by telomerase activity associated with transcriptional activity of human telomerase reverse transcriptase (hTERT), a subunit of telomerase. The dysregulation and reactivation of hTERT gene expression may play an important role in facilitating tumor development. The hTERT promoter region was well identified and is rich in transcription factor binding sites including c-myc, SP1, and esterogen. In our previous study, hTERT polymorphisms, rs2753940 (-1327C&amp;gt;T), rs2853669(-244 T&amp;gt;C), rs2736100 and MNS16A, were examined for lung cancer association study. To identity effect of the hTERT polymorphisms on telomere length and transcriptional activity, we determined telomere length according to hTERT polymorphisms. The two hTERT polymorphisms, rs2753940 (-1327C&amp;gt;T), rs2853669 (-244 T&amp;gt;C), have a significant association with telomere length (P = 0.04, P = 0.013, respectively). This telomere length may be determined by hTERT expression which was regulated promoter polymorphism (rs2853669) by changing of c-MYC binding. We evaluated that rs2853669 is significantly associated with lung cancer prognosis in NSCLCs. Two promoter SNPs have a role in expression of hTERT, which may affect telomere length. These two polymorphisms may be used for risk and prognostic marker of lung 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 5140. doi:1538-7445.AM2012-5140
A1.30 A key role of S100A9 in the pathogenesis of psoriatic arthritis in TTP/S100 deficient mice
Authors: M Fröhling, T Vogl, K Loser, P Paruzel, PJ Blackshear, DJ Stumpo, J Roth, T Pap, A Stratis
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Psoriatic-Arthritis (PsA) is a type of inflammatory chronic arthritis with a seronegative&nbsp;spondyloarthropathy and associated psoriasis. The S100 calcium-binding molecules S100A8 and S100A9, known as damage-associated molecular pattern molecules (DAMP), are highly increased during many inflammatory disorders and their expression correlates with the severity of disease. S100A8 and S100A9 are expressed in low levels in normal epidermis, but are highly expressed in psoriasis. Interestingly a high expression of epidermal S100A8/S100A9 is also an early marker found in patients suffering from systemic onset of juvenile idiopathic arthritis, which has led us to investigate the role of DAMPs under chronic inflammatory conditions. <h3>Material and methods</h3> To analyse the role S100A8 and S100A9 have during inflammation, we crossed S100A9-deficient mice withTTP (tristetraprolin)-deficient mice as a systemic inflammatory model featuring high levels of TNF. Disease progression in TTP-/- x S100A9-/- mice was analysed by immunostaining, immunhistochemistry and the adapted PASI-score. RNA was extracted from snap-frozen mouse tissue for Real-time quantitative PCR analysis. To neutralise TNF in TTP-/- x S100A9-/- mice we used an aTNF-inhibitor monoclonal antibody already in clinical use for therapy of arthritis and psoriasis. To measure altered protein levels we used Western blot analysis. <h3>Results</h3> The loss of S100A9 in TTP-deficient mice leads to highly elevated amounts of S100A8 in the epidermis and furthermore to a severe psoriasis-like phenotype at postnatal day 8. The expression of other effector molecules in the TTP<sup>-/-</sup>/S100A9<sup>-/-</sup> mice know to be involved in the pathogenesis of psoriasis, incuding IL-17, IL-23 and IL-22 is markedly increased compared to TTP<sup>-/-</sup> mice. Treatment withanti-TNF preventedthe mice from developing the psoriatic phenotype, indicating that the psoriasis-like skin disease of TTP<sup>-/-</sup>/S100A9<sup>-/- </sup>mice is tumour necrosis factor (TNF) dependent. <h3>Conclusions</h3> Our results demonstrate that under inflammatory conditions, S100A9 is essential for the regulation of inflammation, suggesting that S100A9 released from epidermal cells may act not &nbsp;only as a systemic danger signal that is involved in the initiation of inflammatory disorders like psoriasis and arthritis, but may also have a homeostatic anti-inflammatory function in the skin.
Abstract 1742: Potential roles of histone deacetylase 11 in cell cycle regulation and cancer.
Authors: Thejal Srikumar, Elphine Telles, Edward Seto
Journal: Cancer Research (2013)

Abstract Histone deacetylases (HDACs) are enzymes that deacetylate lysine residues on histone and non-histone proteins. They regulate various cellular functions including transcriptional regulation, cell proliferation, apoptosis, and cellular metabolism. Broad spectrum HDAC inhibitors, including Vorinostat and Romidepsin, have been approved for cancer therapy, but their use is limited due to toxicity and side effects. A deeper understanding of the function of individual histone deacetylases could lead to the development of more specific and potentially more effective anti-cancer agents. In this context, Histone Deacetylase 11 (HDAC11) could be a potential target for anticancer therapeutics. HDAC11 is the most recently discovered Histone Deacetylase and, therefore, the least characterized among the 18 HDACs. Its expression is altered in various cancers and recent studies have suggested that HDAC11 might inhibit the activity and function of the DNA replication licensing factor Cdt1. To examine whether HDAC11 controls Cdt1-mediated cell cycle regulation, HDAC11 was overexpressed in human U87 glioblastoma cells. We found that overexpression of HDAC11 represses Cdt1 expression levels. Most importantly, we observed that HDAC11 overexpression promotes earlier cell entry into the G2/M phase of the cell cycle than non-HDAC11-overexpressed cells. Finally, we discovered that HDAC11 levels change throughout the cell cycle in a manner that is contrary to the Cdt1 expression levels. These results indicate that HDAC11 negatively regulates Cdt1, and uncover an important and previously unknown role of this enzyme in cell cycle regulation. Together, our findings suggest that development of drugs that target HDAC11 might be a viable strategy for overcoming cancers where this protein is overexpressed. Citation Format: Thejal Srikumar, Elphine Telles, Edward Seto. Potential roles of histone deacetylase 11 in cell cycle regulation and cancer. [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 1742. doi:10.1158/1538-7445.AM2013-1742
A randomized comparison of target-controlled propofol infusion and patient-controlled sedation during ERCP
Authors: Max Mazanikov, Marianne Udd, Leena Kylänpää, Harri Mustonen, Outi Lindström, Martti Färkkilä, Jorma Halttunen, Reino Pöyhiä
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Propofol is widely used during endoscopic retrograde cholangiopancreatography (ERCP) but high doses are recognized as a risk factor for sedation-related complications. The aim of this study was to compare target-controlled infusion (TCI) with patient self-administration (patient-controlled sedation, PCS) of propofol during ERCP. Propofol consumption, the ease of ERCP performance, and speed of recovery were recorded. <b>Patients and methods:</b> A total of 82 patients undergoing elective ERCP were randomized 1:1 to receive propofol 10 mg/mL using TCI (initial targeted effect-site concentration 2 μg/mL) or PCS (single bolus 1 mL, lockout time set at zero). Alfentanil was administered if signs of insufficient analgesia occurred. Consumption of propofol and alfentanil was recorded, sedation levels and vital signs were monitored, the ease of ERCP performance, speed of recovery, and satisfaction with sedation were evaluated. <b>Results</b>: All procedures were performed without interruptions or major sedation-related complications. The mean (± SD) consumption of propofol was 306 ± 124 mg in the TCI group and 224 ± 101 mg in the PCS group (<i>P</i> = 0.002). Patients in the PCS group recovered faster (<i>P</i> = 0.035). The mean (± SD) consumption of alfentanil was 0.5 ± 0.4 mg in both groups. The combination of propofol and alfentanil was associated with an increased risk of sedation-related adverse events (<i>P</i> = 0.031). <b>Conclusions</b>: No benefits of TCI over PCS could be demonstrated in this study. We recommend considering PCS as a feasible option for propofol administration during ERCP because of its ease of use, high success rate, reduced consumption of propofol, and faster recovery.
Equity issues in the NHS: Who cares about equity in the NHS?
Authors: M Whitehead
Journal: BMJ (1994)

The concept of equity in relation to the National Health Service in Britain encompasses not one but at least eight distinct principles. Until the 1980s the NHS had a good record of incorporating these principles into practice. Throughout the 1980s, however, there has been a pronounced change, with the gradual introduction of business values into the service, culminating in the market based reforms of the 1990s. Several recent policies seem to be taking the NHS away from the goal of an equitable system--for example, the new arrangements for community care and the incentives within contracting to select patients on financial grounds. To restore equity as a value demands priority for ethical values, monitoring of policies for their effects on equity, some national planning, and a new debate about the entitlement to services such as continuing care.
Abstract LB-239: Mutational and clonal analyses across TCGA cancer types using the MuSiC suite of tools.
Authors: Cyriac Kandoth, Michael D. McLellan, Christopher A. Miller, Charles Lu, Nathan Dees, Kai Ye, Beifang Niu, Michael C. Wendl, Richard K. Wilson, Li Ding
Journal: Cancer Research (2013)

Abstract Within the field of cancer genomics, advances in next-generation sequencing and variant detection methods have tremendously reduced the costs of generating genomic data for large cohorts of patients in translational cancer research. These large datasets have enabled statistical analyses of somatic events in tumor-normal pairs, with the ultimate goal of understanding the molecular mechanisms underlying various cancer phenotypes. Here, we present results from the suite of tools collectively called MuSiC (Mutational Significance in Cancer), specifically designed towards this goal. Somatic alterations of more than 5000 tumors across 20 cancer types are now publicly available as part of The Cancer Genome Atlas (TCGA). This includes point mutations and small indels from exome sequencing, copy-number variants from SNP arrays, and gene and allele-specific expression from mRNA sequencing. We present results from the suite that integrates these data types to identify significantly altered genes, gene families, protein domains, and pathways. Also presented are the distribution of mutation types, frequencies, and patterns across cancer types, or across histological subtypes of tumors. Further, we identify mutations that can distinguish broader expression and/or methylation subtypes and clinically relevant phenotypes across the combined pan-cancer data set. Finally, we perform clonality analysis across several cancer types by integrating copy number data to identify important mutations that drive the development of new clones. Citation Format: Cyriac Kandoth, Michael D. McLellan, Christopher A. Miller, Charles Lu, Nathan Dees, Kai Ye, Beifang Niu, Michael C. Wendl, Richard K. Wilson, Li Ding. Mutational and clonal analyses across TCGA cancer types using the MuSiC suite of tools. [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 LB-239. doi:10.1158/1538-7445.AM2013-LB-239