tbuckley/cabot-search huggingface dataset:
OP0050 Fine Mapping and Expression of a Locus Overlapping 3 Types of Inflammatory Arthritis
Authors: K. J. A. Steel, A. Hinks, A. Barton, S. Eyre, E. Flynn, P. Martin, W. Thomson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In a recent fine-mapping study using the Immunochip genotyping array, the <i>RUNX1</i> region was associated with rheumatoid arthritis (RA p=5×10<sup>-10</sup>), juvenile idiopathic arthritis (JIA p=1×10<sup>-8</sup>) and psoriatic arthritis (PsA p=6×10<sup>-4</sup>). In each disease the SNP rs9979383 confers disease protection with odds ratios ranging from 0.8-0.9. This SNP maps approximately 290kb upstream of the 3' end of <i>RUNX1</i>, indicating that it may potentially be involved in gene regulation. <i>RUNX1</i> encodes a master transcription factor which has been shown to interact with the regulatory T cell transcription factor <i>FOXP3</i> as well as regulation of skeletal development. Unlike many loci on the Immunochip array, variation in the <i>RUNX1</i> region is not well covered, therefore further fine mapping is required. <h3>Objectives</h3> To fine map the <i>RUNX1</i> region and select a SNP suitable for expression studies. <h3>Methods</h3> As rs9979383 lies between two points of high recombination, SNPs between these points were selected for fine mapping. 42 common (MAF&gt;0.05) tag SNPs (r<sup>2</sup>&gt;0.9) from the Utah residents (CEPH) with Northern and Western European ancestry (CEU) 1000 genomes July 2010 release were selected using Haploview v.4.2. 2255 RA cases and 1877 healthy controls from the United Kingdom Rheumatoid Arthritis Genetics Group (UKRAGG) were genotyped using the Sequenom iPlex MassARRAY platform. SNPs and samples which reached &gt;90% success rate were included in the analysis. Allelic association testing was performed using PLINK v.1.07 and functional annotation of SNPs was performed using the ASSIMILATOR software programme. <h3>Results</h3> In the UKRAG cohort, association with rs9979383 was replicated (p=0.02, OR = 0.9, CI 95% 0.82-0.98) with an odds ratio of 0.9, identical to the previous RA study. No other SNPs in the region showed evidence for association. <i>RUNX1</i> is highly expressed in CD33+ progenitor cells which are important in generation of immune cells and vascularisation of the synovium. Functional annotation of this SNP indicates that it lies within a region of open chromatin with transcription factor binding potential, making it an ideal candidate for gene expression studies. <h3>Conclusions</h3> These results indicate that the <i>RUNX1</i> association is localised to r99793983 in this RA cohort. This will require further investigation in independent JIA and PsA cohorts but provides evidence that the region is associated with different types of inflammatory arthritis. Currently both whole blood and cell specific expression of the <i>RUNX1</i> region are underway using individuals with differential genotypes at rs9979383. Combined with the fine mapping this will inform further investigations of the role of <i>RUNX1</i> in the common pathogenesis of inflammatory arthritis. <h3>Disclosure of Interest</h3> None Declared
Variation in Urinary Flow Rates According to Demographic Characteristics and Body Mass Index in NHANES: Potential Confounding of Associations between Health Outcomes and Urinary Biomarker Concentrations
Authors: Sean M. Hays, Lesa L. Aylward, Benjamin C. Blount
Journal: Environmental Health Perspectives (2015)

Background:Urinary analyte concentrations are affected both by exposure level and by urinary flow rate (UFR). Systematic variations in UFR with demographic characteristics or body mass index (BMI) could confound assessment of associations between health outcomes and biomarker concentrations.Objectives:We assessed patterns of UFR (milliliters per hour) and body weight–adjusted UFR (UFRBW; milliliters per kilogram per hour) across age, sex, race/ethnicity, and BMI category in the NHANES (National Health and Nutrition Examination Survey) 2009–2012 data sets.Methods:Geometric mean (GM) UFR and UFRBW were compared across age-stratified (6–11, 12–19, 20–39, 40–59, and ≥ 60 years) subgroups (sex, race/ethnicity, and BMI category). Patterns of analyte urinary concentration or mass excretion rates (nanograms per hour and nanograms per kilogram per hour BW) were assessed in sample age groups for case study chemicals bisphenol A and 2,5-dichlorophenol.Results:UFR increased from ages 6 to 60 years and then declined with increasing age. UFRBW varied inversely with age. UFR, but not UFRBW, differed significantly by sex (males > females after age 12 years). Differences in both metrics were observed among categories of race/ethnicity. UFRBW, but not UFR, varied inversely with BMI category and waist circumference in all age groups. Urinary osmolality increased with increasing BMI. Case studies demonstrated different exposure–outcome relationships depending on exposure metric. Conventional hydration status adjustments did not fully address the effect of flow rate variations.Conclusions:UFR and UFRBW exhibit systematic variations with age, sex, race/ethnicity, and BMI category. These variations can confound assessments of potential exposure–health outcome associations based on urinary concentration. Analyte excretion rates are valuable exposure metrics in such assessments.Citation:Hays SM, Aylward LL, Blount BC. 2015. Variation in urinary flow rates according to demographic characteristics and body mass index in NHANES: potential confounding of associations between health outcomes and urinary biomarker concentrations. Environ Health Perspect 123:293–300; http://dx.doi.org/10.1289/ehp.1408944
Treatment of the Nephrotic Syndrome with Etanercept in Patients with the Tumor Necrosis Factor Receptor–Associated Periodic Syndrome
Authors: Elizabeth Drewe, Elizabeth M. McDermott, Richard J. Powell
Journal: New England Journal of Medicine (2000)

To the Editor: The tumor necrosis factor (TNF) receptor–associated periodic syndrome is a dominantly inherited, chronic inflammatory condition characterized by lifelong febrile attacks of abdominal and musculoskeletal pain associated with skin lesions. The attacks vary in severity and in frequency, usually last from 3 to 21 days, and respond to high-dose corticosteroids. Soluble TNF receptors can inhibit TNF activity by binding and preventing the interaction of TNF-α (TNFSF2) with its cell-surface receptor. Recombinant human TNF receptor (TNFRSF1B) (p75):Fc fusion protein (etanercept) inhibits the activity of TNF in vitro and reduces inflammation in animal models.1 We evaluated a woman with the . . .
The Effect of Triethylene Melamine, Aureomycin, and Some 4-Amino Derivatives of Folic Acid on Tissues &lt;italic&gt;in Vitro&lt;/italic&gt;&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Grace Antikajian, Ph. D., Louis T. Wright, M. D., Jewel I. Plummer, Ph. D., Solomon Weintraub, M. D.
Journal: JNCI Journal of the National Cancer Institute (1951)

Journal Article The Effect of Triethylene Melamine, Aureomycin, and Some 4-Amino Derivatives of Folic Acid on Tissues in Vitro Get access Grace Antikajian, Ph. D., Grace Antikajian, Ph. D. Cancer Research Foundation, Harlem Hospital, New York, N. Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Louis T. Wright, M. D., Louis T. Wright, M. D. Cancer Research Foundation, Harlem Hospital, New York, N. Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jewel I. Plummer, Ph. D., Jewel I. Plummer, Ph. D. Cancer Research Foundation, Harlem Hospital, New York, N. Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Solomon Weintraub, M. D. Solomon Weintraub, M. D. Cancer Research Foundation, Harlem Hospital, New York, N. Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 2, October 1951, Pages 269–274, https://doi.org/10.1093/jnci/12.2.269 Published: 01 October 1951 Article history Received: 15 February 1951 Published: 01 October 1951
PTU-106 Patient Impact of Inflammation in Primary Biliary Cirrhosis (Pbc): Inflammatory Cytokine Levels are Elevated but Unrelated to Fatigue Severity
Authors: G Pells, S Ducker, J Palmer, J Newton, D Jones
Journal: Gut (2013)

<h3>Introduction</h3> PBC is characterised by loss of small intrahepatic bile ducts, and in a significant proportion of patients by persistent fatigue. Genes regulating inflammatory pathways have been strongly associated with PBC in population-scale genetic studies, implicating inflammation in disease pathogenesis. Animal models of cholestasis, a biological process in PBC, have demonstrated fatigue-like behaviour appearing to result from responses to inflammatory cytokine release in the brain. Elevation of inflammatory cytokines has therefore, unsurprisingly, been postulated as an underlying mechanism for fatigue in PBC as well as other chronic inflammatory conditions. However, more recently data demonstrating that fatigue is not proportional to liver disease severity in PBC has questioned this presumed correlation between inflammation and fatigue. This study aimed to explore the serum cytokine profile in PBC compared to healthy controls, and to correlate this picture of inflammation status with fatigue severity. <h3>Methods</h3> 68 patients from the Newcastle sector of the UK-PBC cohort and 9 healthy controls provided a morning peripheral blood sample and completed the PBC-40, a validated disease-specific quality of life measure with a fatigue domain. Sera were derived using standard protocols and stored at –80°C prior to multiplex cytokine quantification using the MSD platform. <h3>Results</h3> PBC patients showed significant elevation of IFN-γ (median 2.4pg/ml[IQR 1.6–15.4] v control 0.7[0.2–1.5], p &lt; 0.0005), IL-6 (1.0pg/ml[0.4–3.3] v 0.5[0–1.5],p &lt; 0.005) and TNF-α (7.1pg/ml[5.5–10.5] v 4.3[3.6–5.9],p &lt; 0.001). IL-1β was elevated in patients but fell short of significance (2.3 pg/ml [0.2–2.3] v 0.5[0.1–0.8],p = ns). Within the PBC group cytokine levels were compared between 21 patients reporting mild fatigue (established using published cut-offs for PBC-40 fatigue domain severity) and 24 patients with severe fatigue. No significant differences were seen between mildly and severely fatigued patients, and for three of the four pro-inflammatory cytokines (IFN-γ,IL-1β and TNF-α) levels were in fact lower in severely fatigued patients. <h3>Conclusion</h3> Serum inflammatory cytokine levels are significantly elevated in PBC, in keeping with inflammation playing a key role in disease pathogenesis. Although the study protocol cannot exclude central nervous system-specific inflammatory mechanisms, no evidence was found to implicate inflammation in the pathogenesis or expression of fatigue in PBC, suggesting a further factor independent of inflammatory disease pathogenesis predisposes certain patients to fatigue. <h3>Disclosure of Interest</h3> None Declared.
Royal prerogative: having it both ways?
Authors: Nick Ross
Journal: Journal of the Royal Society of Medicine (2013)

Is it all right to argue with the Prince of Wales? Or, if not treasonable is it disrespectful? I hope not because while there is nothing wrong with our future king being consensual or imperious (and what is the point of monarchy without a bit of imperium?), if he wishes to engage in controversy he should be prepared to engage in debate like everybody else.

He seems a good man with good intentions. No doubt so were the wise ancients who believed disease was punishment from the gods or caused by disturbances in humours or meridians. So were the inventors of thalidomide.

The problem is that Charles wants science when it comes up with the answers he wants but anecdote and spiritualism when it does not.

In so-called conventional medicine it is not ethical to give people treatments that have been shown not to work. Is he proposing that we should give patients treatments for which there is no empirical proof of efficacy, and do so without coming clean to them about disappointing contra-evidence?

As for compassion, yes resources are squeezed and sadly that can mean compassion is sometimes marginalized. But the National Health Service remains the most popular institution in Britain because on the whole it cares for people very well.

What we can all agree on is the interconnectedness of injury, disease, pain, unhappiness and lack of self-esteem. That is why science has led to treatments that go beyond the physical including cognitive-behavioural therapy. But that does not mean vaccination was only a partial treatment for smallpox, or that Paracetamol is not normally the only necessary remedy for headaches.

HRH has more influence than most. It is a shame he uses it to promote ‘integrative’ health which really seeks to insinuate preEnlightenment quackery back into mainstream medicine.
P887 POST LIVER TRANSPLANTATION PROPHYLAXIS OF HEPATITIS B RECURRENCE WITH NUCLEOS(T)IDE ANALOG THERAPY FOLLOWING HEPATITIS B IMMUNOGLOBULIN DISCONTINUATION
Authors: I. Fernández, M. Abradelo, O. Hernández, C. Loinaz, M. Alejandro, M.L. Manzano, A. García, J. Calvo, F. Cambra, C. Jimenez
Journal: Journal of Hepatology (2014)
AB0213 Alleviation of nephritis in lupus-prone NZB/WF1 mice by a combination treatment of thalidomide plus prednisolone
Authors: S.-W. Lee, Y.-B. Park, J. Yang, K.-H. Park, S.-K. Lee, K.H. Choi, B.S. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Proliferative lupus nephritis (Class III and IV) is the most severe form of lupus nephritis. The use of intravenous or oral prednisolone (PL) plus either intravenous cyclophosphamide or oral mycophenolate mofetil (MMF) currently is recommended as the standard induction therapy for proliferative lupus nephritis. However, despite improved outcomes with these induction therapies, end-stage renal disease still occurs in up to 30% of patients over a 20-year disease course. Thus, a new therapeutic modality is necessary. Thalidomide is a drug to treat multiple myeloma. Thalidomide can modulate NF-κB activity in myeloma cells, resulting in up-regulating pro-apoptotic regulators and down-regulating anti-apoptotic proteins. Recently, NF-κB was rediscovered to regulate mesangial proliferation in lupus-prone mice. Thus, considering the action-mechanism of thalidomide and its well-established efficacy in multiple myeloma, thalidomide could be an additional treatment for lupus nephritis, comparable to current regimes. <h3>Objectives</h3> We first investigated the efficacy of thalidomide on nephritis in lupus-prone mice and compared it to mycophenolate mofetil plus prednisolone. <h3>Methods</h3> Forty-three female NZB/WF1 mice were divided into eight groups (untreated; 1.7, 5, or 10 mg/kg of thalidomide alone; 1.7, 5, or 10 mg/kg of thalidomide plus prednisolone; and mycophenolate mofetilplus prednisolone). Proteinuria and histological damages were evaluated. Immune-complex deposition and nuclear translocation of NF-κB in kidney tissues were assessed by immunofluorescence staining. Serum concentration of anti-ds DNA and immunoglobulin G subclasses were also measured. <h3>Results</h3> In comparison with untreated mice, mice treated with 5 or 10 mg/kg of thalidomide plus prednisolone, or mycophenolate mofetilplus prednisoloneshowed a significant decrease in proteinuria and significantly lowered glomerular and tubular damage scores. Treatment with either 5 or 10 mg/kg of thalidomide plus prednisolone or mycophenolate mofetil plus prednisolone significantly decreased immune-complex accumulation, reduced the serum concentration of anti-ds-DNA, IgG2a, IgG2b and IgG3, and inhibited nuclear translocation of NF-κB in kidney tissues, compared to no treatment. <h3>Conclusions</h3> Thalidomide plus PL combination therapy significantly attenuated nephritis in lupus-prone mice. Thalidomide plus PL decreased the serum concentration of anti-ds DNA and IgG subclasses, and reduced glomerular deposition of immune complexes. Also they inhibited nuclear translocation of NF-kB and finally alleviated both proteinuria and histological renal damage. These data suggest that thalidomide plus PL might be anti-inflammatory in lupus nephritis pathophysiology and could serve as an additional therapy for lupus nephritis. <h3>Disclosure of Interest</h3> None Declared
Diagnosis and Management of Facial Paralysis
Authors: Kedar K. Adour
Journal: New England Journal of Medicine (1982)

DISEASES affecting the facial nerve present problems to physicians in all branches of medicine. Information on the facial nerve is scattered throughout the textbooks and journals of many specialties, and controversy exists: there is no agreement on diagnosis, prognosis, or therapy in cases of acute facial paralysis. Much of the disagreement can be traced to faulty premises — i.e., to incomplete knowledge of the pathophysiology of facial paralysis and to the lack of neurodiagnostic tests to indicate the pathology at any time during the course of the facial paralysis.The facial nerve was initially considered to be the nerve most . . .
Assessment and Management of Foot Disease in Patients with Diabetes
Authors: Gregory M. Caputo, Peter R. Cavanagh, Jan S. Ulbrecht, Gary W. Gibbons, Adolf W. Karchmer
Journal: New England Journal of Medicine (1994)

The human and financial costs of lower-extremity amputation in patients with diabetes mellitus are well recognized1. However, the rates of major amputation in the United States remain high,2 in part because present knowledge regarding the prevention and management of foot disease is not widely applied in clinical practice. The U.S. Department of Health has set a goal for the year 2000 of a 40 percent reduction in amputation rates among diabetic patients3. Methods to achieve this goal are available today. For example, in the majority of diabetic patients, the initial condition that eventually leads to amputation is a . . .
Abstract 2309: Identification and targeting of small noncoding RNAs implicated in tumor angiogenesis.
Authors: Albert S. Mellick, Prue N. Plummer, Vivek Mittal
Journal: Cancer Research (2013)

Abstract Bone marrow (BM)-derived endothelial progenitor cells (EPCs) contribute to angiogenesis-mediated tumor growth. In previous studies[1], we showed that EPCs can be tracked from the BM to sites throughout the body, including the BM compartment of the tumor stroma. We also demonstrated that the Inhibitor of DNA binding 1 (ID1) proximal promoter can be used to silence genes in EPCs, through directed delivery of short hairpin RNA inhibition. Here we report the elucidation of a novel small RNA pathway regulated by miR-10b, required for regulation of EPC function and tumor angiogenesis. We demonstrate that this pathway is required for tumor vascular biology and through in situ hybridization (ISH) that it is preferentially up-regulated in the vasculature of aggressive late stage Infiltrating Ductal Carcinomas, and not in more contained Ductal Carcinomas. Such analysis reveals the clinical implications of in vivo targeting of miRNAs, such as miR-10b in cancer therapeutics, and reveals the need for cell specific localisation of miRNA expression in understanding tumor malignancy.[2] 1. Mellick AS, Plummer P, Nolan D, et al. Using Transcription Factor Id1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth. Cancer Res. 70:7273-82, 2010. 2. Plummer PN, Freeman R, Taft R, Vider J, Sax M, Umer BA, Gao D, Johns CA, Mattick JS, Wilton SD, Ferro V, McMillan NA, Swarbrick A, Mittal V, Mellick AS. MicroRNAs regulate tumor angiogenesis modulated by endothelial progenitor cells. Cancer Res. 2012 Jul 25. [Epub ahead of print]. Citation Format: Albert S. Mellick, Prue N. Plummer, Vivek Mittal. Identification and targeting of small noncoding RNAs implicated in tumor angiogenesis. [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 2309. doi:10.1158/1538-7445.AM2013-2309
Abstract 3479: Targeting FoxM1 selectively depletes hepatic cancer stem cells
Authors: Dragana Kopanja, Pradip Raychaudhuri
Journal: Cancer Research (2012)

Abstract Over-expression of the Forkhead box M1 (FoxM1) transcription factor coincides with highly aggressive, poorly differentiated hepatocellular carcinoma (HCC). Over-expression of FoxM1 in HCC also correlates with poorer overall survival after hepatectomy. Since HCC progression involves hepatic cancer stem cells (HCSCs), we considered the roles of FoxM1 in HCSCs. We found that FoxM1 expression correlates with the expression of the stemness genes in human HCC cell lines. Interestingly, depletion of FoxM1 in human HCC lines causes a selective reduction in the population of the CD90+ HCSCs due to selective apoptosis. Moreover, FoxM1 silencing decreases sphere formation potential of the same cell lines, suggesting that FoxM1 is critical for survival of the HCSCs. Consistent with the loss of HCSCs, depletion of FoxM1 causes decrease in tumorigenic potential of the HCC cells in vitro as well as inhibition of tumor formation in mouse xenografts. Furthermore, we found that FoxM1 directly regulates expression of CD44, previously shown to be important for the tumorigenic potential of CD90+ HCC cells. These studies have exciting implications in further considerations of FoxM1 as a target of HCC therapy. 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 3479. doi:1538-7445.AM2012-3479
Abstract 5425: The catalytic subunit of DNA-dependent protein kinase is downstream of ATM and feeds forward oxidative stress in selenium-induced senescence response
Authors: Wen-Hsing Cheng, Caroline R. Rocourt, Min Wu, Benjamin P. Chen
Journal: Cancer Research (2012)

Abstract Selenium induces a senescence response through induction of ataxia-telangiectasia mutated (ATM) and reactive oxygen species (ROS). Although a role of the DNA-PK complex, including the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), Ku70 and Ku80, in DNA double strand break repair is established, it is unclear how these proteins function in the response to selenium-induced oxidative stress and senescence induction. In this study we demonstrate that pre-treating normal human diploid fibroblasts with DNA-PK kinase inhibitor NU 7026 suppresses selenium-induced senescence response. Selenium treatment induces phosphorylation of DNA-PKcs on Thr-2647 and Ser-2056, the extent of which is decreased in the presence of ATM kinase inhibitor KU 55933 or the antioxidant N-acetylcysteine or 2,2,6,6-tetramethylpiperidine-1-oxyl. In contrast, the selenium-induced phosphorylation of ATM on Ser-1981 is not affected by NU 7026. Cells deficient in DNA-PKcs or pre-treated with NU 7026 or N-acetylcysteine are defective in selenite-induced ROS formation. Opposed to DNA-PKcs, Ku70 and Ku80 are dispensable for selenite-induced ROS and γH2A.X formation and removal. Taken together, these results indicate a distinct role of DNA-PKcs from Ku70 and Ku80, in which this kinase can respond to and feed forward selenium-induced ROS formation and is placed downstream of ATM in the resultant senescence response. 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 5425. doi:1538-7445.AM2012-5425