tbuckley/cabot-search huggingface dataset:
AB0058 A simple set of validation steps identifies and removes false positive measurements in a sandwich elisa caused by anti-animal protein antibodies in arthritis plasma
Authors: T. W. Kragstrup, T. Andersen, B. Deleuran, T. V. Jensen, M. H. Larsen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In spite of the widespred use of sandwich ELISAs in arthritis research recommendations on how to eliminate unspecific interference by rheumatoid factor and anti-animal protein antibodies frequently found in arthritis plasma are lacking. <h3>Objectives</h3> The objective of this study was to design a simple set of steps for validating and optimizing a sandwich ELISA before using it for measuring arthritis plasma. As an example of an immunoassay for arthritis research an anti-IL-24 sandwich ELISA system was prepared with a monoclonal mouse capture antibody and a polyclonal goat detection antibody. <h3>Methods</h3> Plasma samples from patients with rheumatoid arthritis and spondyloarthritis were analyzed. A simple set of validation steps identified signals from samples in wells coated with isotype matched control antibody (false positive results) and lack of recovery after spiking samples (false negative results). ELAST<sup>®</sup> (Perkin Elmer) amplification kit was used to amplify HRP signal before addition of substrate. <h3>Results</h3> Interference was removed after preincubating the arthritis plasma samples with goat or bovine IgG (10 µg/ml – 100 µg/ml), suggesting that anti-animal protein antibodies found in the plasma of the arthritis patients caused the false results. Additional testing showed that an amplification step, using ELAST could increase the signal-to-noise ratio. Furthermore we show that repetitive freeze-thaw cycles of the samples, the anticoagulant used in the samples and the buffer used for the standard curve could affect the calculated concentration of the analyte. <h3>Conclusions</h3> This study establishes an in-house sandwich ELISA system and validates it for measuring arthritis plasma with a simple set of validation and optimization steps removing the anti-animal antibodies cross binding of capture and detection antibodies. Any sandwich ELISA to be used in arthritis research could be validated an optimized by a similar setup. <h3>Disclosure of Interest</h3> None Declared
Credit Due in Oncologic Therapeutics
Authors: R. E. WITTES
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Credit Due in Oncologic Therapeutics Get access ROBERT E. WITTES ROBERT E. WITTES Bristol-Myers Co.5 Research Parkway P.O. Box 5100 Wallingford, CT 06492-7660 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 15, 2 August 1989, Page 1194, https://doi.org/10.1093/jnci/81.15.1194 Published: 02 August 1989
Changes in Plasma Lipids and Lipoproteins in Overweight Men during Weight Loss through Dieting as Compared with Exercise
Authors: Peter D. Wood, Marcia L. Stefanick, Darlene M. Dreon, Barbara Frey-Hewitt, Susan C. Garay, Paul T. Williams, H. Robert Superko, Stephen P. Fortmann, John J. Albers, Karen M. Vranizan, Nancy M. Ellsworth, Richard B. Terry, William L. Haskell
Journal: New England Journal of Medicine (1988)

We studied separately the influence of two methods for losing fat weight on the levels of plasma lipids and lipoproteins in overweight sedentary men — decreasing energy intake without increasing exercise (diet), and increasing energy expenditure without altering energy intake (exercise, primarily running) — in a one-year randomized controlled trial. As compared with controls (n = 42), dieters (n = 42) had significant loss of total body weight (-7.8±0.9 kg [mean ±SE]), fat weight (-5.6±0.8 kg), and lean (nonfat) weight (-2.1±0.5 kg) (P<0.001 for each variable), and exercisers (n = 47) had significant loss of total body weight (-4.6±0.8 kg) and fat weight (-3.8±0.7 kg) (P<0.001 for both variables) but not lean weight (-0.7±0.4 kg). Fat-weight loss did not differ significantly between dieters and exercisers. All subjects were discouraged from altering their diet composition; however, dieters and exercisers had slight reductions in the percentage of kilojoules derived from fat. As compared with the control group, both weight-loss groups had significant increases (P<0.01) in plasma concentrations of high-density lipoprotein (HDL) cholesterol (diet vs. exercise, 0.13±0.03 vs. 0.12±0.03 mmol per liter), HDL2 cholesterol (0.07±0.02 vs. 0.07±0.02 mmol per liter), and HDL3 cholesterol (0.07±0.02 vs. 0.06±0.02 mmol per liter) and significant decreases (P<0.05) in triglyceride levels (diet vs. exercise, -0.35±0.14 vs. -0.24±0.12 mmol per liter). Levels of total and low-density lipoprotein cholesterol were not significantly changed, relative to values in controls. None of these changes were significantly different between dieters and exercisers. Thus, we conclude that fat loss through dieting or exercising produces comparable and favorable changes in plasma lipoprotein concentrations. (N Engl J Med 1988; 319:1173–9.)
P177 Are NIV supported PEG insertions (NSPI) in patients with neuromuscular degenerative disorders (NMD) safe and effective?
Authors: J Rafique, P Luck, N Chaudhry, A Bentley
Journal: Thorax (2013)

<h3>Introduction</h3> Patients with NMD9s suffer from feeding difficulties and respiratory failure which worsens prognosis. A survival advantage with PEG feeding has been suggested in case reports but there are concerns regarding safety and complications in this high risk group in or at risk of ventilatory failure. We have therefore reviewed the outcomes of NSPIs in our tertiary teaching hospital. <h3>Methods</h3> 33 NSPIs were identified upto 2012. Disease background, baseline lung physiology, NIV use, peri-procedure details, complications and survival at 365 days were analysed. A subset analysis examining bulbar vs. non bulbar MND, baseline FVC and NIV use against survival at 365 days was also carried out. <h3>Results</h3> 33 patients with NMD (MND 79%, DMD 9%, Myotonic Dystrophy 6%, others 6%) were included. Mean age was 59 (range 21–80). Mean pre-procedure FVC was 57% ( 22–95 ), SNIP was 3.9kPa (1.8–6.2kPa). Mean pre-procedure pO<sub>2 </sub>was 10kPa (7.3–12.4), pCO<sub>2</sub> 5.7kPa (4.2–7.5) and HCO<sub>3</sub> 27.6mmol/L (23.8–31). 52% were previously on NIV. Mean pre-procedure NIV settings were IPAP 18cmH20, EPAP 3cmH20. Mean post procedure settings were 19 and 3cmH20 respectively. 11% needed supplemental oxygen for a short period post procedure. Sedation was used in 95% and no medical reversals were needed. Complication rates were 9%, 3%, 10% and 9% (immediate, 6 weeks, 6 months, 1yr) respectively. Of those who were NIV naïve initially, 13% went home established on NIV. Survival at 365 days post procedure was 64%. Subset analysis of outcomes in bulbar vs. non-bulbar MND, FVC &lt; or &gt; 50% and NIV for procedure only vs. discharge with NIV has not shown any statistically significant differences, although absolute numbers are small. <h3>Conclusions</h3> High risk NMD patients can have PEGs inserted safely. Our complications and one year survival rates are better compared with current published evidence in lower risk groups. We believe this is due to intensive support and monitoring during the procedure and use of NIV. Although survival is largely related to disease progression, further analysis is required with larger numbers to fully assess the impact of PEG feeding on it.
RELATIVE PERFORMANCE OF SPECT AND PET MYOCARDIAL PERFUSION IMAGING IN A PROSPECTIVELY RANDOMIZED POPULATION OF SYMPTOMATIC PATIENTS WITH KNOWN CORONARY ARTERY DISEASE
Authors: Timothy M. Bateman, Iain A. McGhie, Gary Heller, Staci Courter, Eric Burgett, James Case
Journal: Journal of the American College of Cardiology (2016)
PMO-132 Histone variant macroh2a1 knock-out worsens high fat diet-induced systemic insulin resistance, glucose intolerance and hepatic steatosis in mice
Authors: M Vinciguerra, C Podrini, A Greco
Journal: Gut (2012)

<h3>Introduction</h3> Hepatic steatosis is a major risk factor for the development of severe liver damage, including fibrosis, cirrhosis and hepatocellular carcinoma. It often exists as a co-morbidity factor with diabetes type I/II and with other manifestations of the metabolic syndrome. Recent studies highlight the importance of an epigenetic basis for the development of steatosis based on macroH2A1. MacroH2A1 is a histone variant of histone H2A, which possesses an additional protein domain called macro. When incorporated into the chromatin of hepatocytes, macroH2A1 regulates gene expression. Two alternatively spliced isoforms of macroH2A1 exist, which have been shown to be markers of breast, skin and lung cancer. Whole-body knock out of macroH2A1 in mice induces glucose intolerance and changes in genes regulating hepatic lipid metabolism. However, overt hepatic steatosis was not observed and the significance of these findings is unclear. We hypothesised that macroH2A1 could be involved in the pathogenesis of hepatic steatosis induced in the high fat-diet mouse model of metabolic syndrome. <h3>Methods</h3> Wild type and homozygous knock-out male mice were placed on a high fat diet (Western diet, 42% of energy intake from saturated fats) for 8 weeks. At the end of the treatment, measurement of insulin sensitivity and glucose tolerance (ITT and GTT) were performed. Mice were sacrificed, and plasma and liver tissue harvested for further assays, including protein, gene expression and immunohistochemistry analyses. <h3>Results</h3> Deterioration in insulin resistance and glucose intolerance induced by high fat diet was observed in macroH2A1 knock-out mice, compared to wild type littermates. Moreover, lack of macroH2A1 in mice significantly worsened the increase in circulating non-esterified fatty acids (NEFA) and the hepatic intracellular content of tryglicerides induced by high fat diet. Gene expression studies unveiled an increase in the hepatic expression of lipoprotein lipase (Lpl) and fatty acid transporter CD36 in knock-out mice. <h3>Conclusion</h3> MacroH2A1 is a regulator of hepatic fat accumulation and its absence worsens hepatic steatosis and systemic imbalances upon a high fat regimen in mice. This could be due to a direct effect of macroH2A1 on chromatin structure and on the expression of key genes involved in liver lipid metabolism. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Changolkar LN</b>, Costanzi C, Leu NA, <i>et al</i>. Developmental changes in histone macroH2A1-mediated gene regulation. <i>Mol Cell Biol</i> 2007;<b>27</b>:2758–64. 2. <b>Boulard M</b>, Storck S, Cong R, <i>et al</i>. Histone variant macroH2A1 deletion in mice causes female-specific steatosis. <i>Epigenetics Chromatin</i>. 2010;<b>3</b>:8.
SP0213 Clinical and Pathogenetic Aspects of Autoinflammatory Syndromes
Authors: J.W. Van Der Meer
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Some 15 years ago, the term autoinflammatory syndrome has been coined to delineate a group of disorders in which patients suffer from recurrent or chronic inflammation without an obvious exogenous trigger. In earlier days, these syndromes were described as periodic or episodic fevers; the most prominent among these are Familial Mediterranean fever (FMF), TNF receptor associated periodic syndrome (TRAPS), Hyper-IgD syndrome (HIDS) and Cryopyrin-associated periodic syndrome (CAPS). Today, some 15 different autoinflammatory disorders have been recognised as autoinflammatory syndromes. Elucidation of the genetic background, using modern genetic techniques, has taught a lot about the inflammatory pathways in many these disorders. Baseline activation of inflammasomes (hetero- and homo-multimeric protein complexes that trigger cytokine activation) appears to play a role in many of these disorders. Among the cytokines that are activated, especially interleukin-1beta (IL-1beta) stands out. This is further corroborated by a beneficial effect of therapeutic interventions directed towards IL-1beta, using either recombinant IL-1 receptor antagonist (anakinra), soluble decoy receptor construct (rilonacept) or neutralising monoclonal antibody against IL-1beta. We are now at a stage where it is realised that not all autoinflammatory syndromes respond in the same way to IL-1 blockade, pointing to the complexity of the cytokine network and the role of pro-inflammatory cytokines other than IL-1beta. Originally, a sharp distinction was made between autoinflammatory syndromes and autoimmune disorders. In the former, autoreactive T- and/or B-lymphocytes, which are a hallmark of autoimmunity, were thought to be absent. By the recognition of syndromes with autoinflammatory and autoimmune traits, this distinction has become less strict. This also implies that not all autoinflammatory syndromes are pure disorders of an overactive innate immune system. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6325
Epiphyseal Injury Following Frostbite
Authors: Jack R. Dreyfuss, Melvin J. Glimcher
Journal: New England Journal of Medicine (1955)

BONE changes in frostbitten extremities have been described only rarely in the medical literature, and before World War II, most cases documented by radiographic studies were from Europe. In a recent article Vinson and Schatzki1 carefully reviewed the x-ray findings in 100 soldiers who received frostbite injuries during the Korean conflict. Sixty-four of the patients, all young men whose epiphyses were already fused, showed some abnormality of bone during the period of x-ray observation. The case presented below, that of a child of seven, seems worth recording because of the striking roentgenographic changes demonstrated in a hand that had been . . .
Abstract 1335: Immune regulation in endometriosis and epithelial ovarian cancer
Authors: Gina M. Mantia-Smaldone, Raluca Budiu, Suketu Mansuria, Ted Lee, Kristin Zorn, Esther Elishaev, Robert P. Edwards, Anda Vlad
Journal: Cancer Research (2010)

Abstract Objective: Examine the expression and immunogenicity of a known ovarian tumor-associated antigen, MUC1, in ectopic endometriosis lesions and epithelial ovarian cancer (EOC). Determine whether an imbalance in CD4 T cell subsets contributes towards endometriosis pathogenesis and ovarian carcinogenesis. Methods: Biologic specimens were obtained from women with endometriosis, endometriosis-related (endometrioid and clear cell) or serous EOC, and healthy controls, according to University of Pittsburgh IRB protocols. MUC1 and immune cell expression were determined via immunohistochemistry (IHC). Anti-MUC1 IgM and IgG antibody levels were determined via ELISA. Peripheral blood mononuclear cells and cryopreserved cell suspensions from tissue lesions were immunophenotyped using multicolor flow cytometry. Stroma and epithelial cells from tissue biopsies were collected by laser capture microdissection (LCM) and examined with immune-based quantitative RT-PCR arrays. Results: MUC1 was overexpressed in 67% of endometriosis and 89% of EOC lesions. Women with early or late stages of endometriosis had significantly higher anti-MUC1 IgM responses when compared to those women with endometriosis-related EOC (25.3 % of positive control vs.14.2%, p=0.03; 26.3 vs. 14.2%, p=0.04) and to those with serous EOC (25.3 vs. 14.6%, p=0.04; 26.3 vs.14.6%, p=0.04). Women without disease also had significantly higher anti-MUC1 IgM responses compared to endometriosis-related (29.2 vs.14.2%, p=0.01) and serous EOC (29.2 vs.14.6%, p=0.02). Immune cells, including CD3, CD4, and CD8 T cells, are present in endometriotic lesions and appear more abundant than in eutopic endometrium. Flow cytometric analysis of endometriotic lesion-infiltrating T cells revealed a decrease in the frequency of IFN-γ CD4 and CD8 T cells, similar to that seen in patients with EOC. Conclusions: MUC1 is present and appears to be overexpressed in ectopic endometriotic and EOC lesions. Women with endometriosis-related EOC or with serous EOC had significant lower anti-MUC1 IgM levels, suggesting that a compression of antigen-specific humoral (i.e., Th2 driven) immunity may play a role in carcinogenesis. Endometriotic and EOC lesions also appear to have diminished Th1 immunity, suggesting a possible role for local immune suppression. Quantitative analyses of several immune genes in the lesion microenvironment are currently ongoing and will potentially contribute to immune biomarker discovery and improvements in the early detection and prevention of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1335.
SIMILARITIES IN CORONARY FUNCTION AND MYOCARDIAL DEFORMATION BETWEEN PSORIASIS AND CORONARY ARTERY DISEASE: THE ROLE OF OXIDATIVE STRESS AND INFLAMMATION
Authors: Ignatios Ikonomidis, George Makavos, Evangelia Papadavid, Maria Varoudi, Ioanna Andreadou, Kostas Gravanis, George Pavlidis, Leonidas Palaiodimos, Helen Triantafyllidi, John Parissis, Ioannis Paraskevaidis, Dimitrios Rigopoulos, John Lekakis
Journal: Journal of the American College of Cardiology (2015)
Pediatric Hospitalizations Due to Influenza in 2010 in Argentina
Authors: Romina Libster, Silvina Coviello, Maria L. Cavalieri, Adriana Morosi, Nora Alabart, Liliana Alvarez, Fernando Ferrero, Kathryn M. Edwards, Fernando P. Polack
Journal: New England Journal of Medicine (2010)

To the Editor: Much concern has been raised about the upcoming 2010–2011 flu season in the Northern Hemisphere. In preparation for this event, we investigated the burden of influenza during the 2010 season in the Southern Hemisphere in the same hospitals involved in our report in the Journal (Jan. 7 issue)1 of serious disease in children in Argentina during the 2009 season. During 2009, Argentina had the third largest number of deaths due to pandemic influenza in the Americas.2 As reported in the Journal, 1 our retrospective case series consisted of 251 hospitalizations and 13 deaths between May 1 and July . . .
AB0703 The association of quality of life with anxiety, depression, somatization and clinical features in systemic lupus erythematosus patients
Authors: Ö. Pamuk, S. Dönmez, A.M. Onat, B. Kisacik
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The quality of life (QoL) is seriously impaired in patients with systemic lupus erythematosus (SLE). In addition to activity and damage indexes, new scoring systems evaluating QoL in SLE have come into use recently. <h3>Objectives</h3> In our study, we tested the validity of the Turkish version of Lupus-QoL score; and we determined its association with clinical findings and activity indexes. <h3>Methods</h3> We included 64 female patients (mean age: 38.2±11.7 years) diagnosed with SLE according to ACR 1987 criteria. Patients' clinical and demographic features, biochemical test results were obtained from hospital files. SLE disease activity (SLEDAI) was determined concomitantly with the administration of Lupus-QoL questionnaire. Lupus-QoL was comprised of a total of 34 questions which were about (8 questions), (6 questions), (5 questions), (3 questions), (3 questions), (4 questions), (2 questions), and (3 questions). The patients replied these questions pertaining to their previous week as " " (0-4 points). In addition, the patients answered the hospital anxiety (HADS-A), depression scales (HADS-D) and their somatization symptom scores (SSC) were determined. <h3>Results</h3> Renal involvement was present in 23 patients, 10 had neurologic involvement and 30 had hematological findings. Patient age correlated with HADS-A score (r=0.38, p=0.011) and SSC scores (r=0.3, p=0.05). Disease duration correlated with pain-related score (r=0.37, p=0.015), intimate contact (r=0.39, p=0.05). SLEDAI score had a negative correlation (r=-0.34, p=0.025) with intimate contact. SLE patients who admitted to having Raynaud had significantly higher HADS-D scores than others (7.04±4.3 vs. 3.7±3.8, p=0.016). SLE patients with renal involvement had significantly higher planning score (42.6±23.4 vs. 27±22.9, p=0.033) and HADS-D score (7.4±4.9 vs. 4.2±3.1, p=0.016) score. SLE patients with a positive anti-dsDNA antibody had significantly higher SLEDAI scores; physical health (48.8±41.3 vs. 77.4±51.7, p=0.049), intimate contact (43.5±49.6 vs. 85.7±67.7, p=0.023), burden to others (34.5±33 vs. 60.9±38.8, p=0.028), HADS-A score (6.14±3.9 vs. 10.04±4.1, p=0.003), and SSC score (1.14±1.5 vs. 3.04±1.9, p=0.001) were significantly lower. In the antinucleosome-positive group, SSC score was significantly lower (0.71±1 vs. 2.4±2, p=0.003). <h3>Conclusions</h3> QoL score is seriously impaired in SLE patients especially for patients with severe disease manifestations. <h3>Disclosure of Interest</h3> None Declared
NT-03 * DRAMATIC RESPONSE INDUCED BY VEMURAFENIB IN A BRAF V600E-MUTATED BEVACIZUMAB REFRACTORY GLIOBLASTOMA
Authors: L. Arvanitis, C. Marchioli, J. Flickinger, A. Pritchard, J. Engh, N. Amankulor, F. Lieberman, M. Nikiforova, G. Murdoch, J. Drappatz
Journal: Neuro-Oncology (2014)

A significant number of patients with high-grade gliomas do not respond to standard therapy. For relapsed bevacizumab refractory Glioblastoma (GBM), no effective treatment options exist. Recently, BRAF V600 mutations have been recognized in higher frequency in younger patients with epithelioid GBM (E-GBM) and other primary brain tumors. We describe the case of a 40 year old Caucasian woman with left temporal epithelioid GBM who originally presented at age 39 with seizures. She underwent gross total resection followed by external beam radiation with concurrent temozolomide and two cycles of adjuvant temozolomide. Her tumor recurred 5 months from diagnosis and she underwent radiosurgery followed by bevacizumab. Four months later she developed marked interval radiographic progression associated with a severe non-fluent aphasia. Because molecular analysis of the primary tumor revealed a BRAF V600E mutation, she was placed on the BRAF inhibitor vemurafenib. After only two months of vemurafenib therapy we observed a robust partial radiographic response along with complete recovery of language and return to near normal neurologic function. While not a common mutation, there may be a role for BRAF inhibitors in a subset of GBM with BRAF V600 mutations. BRAF V600E mutational analyses should be performed on GBMs, and prospective trials are warranted.