tbuckley/cabot-search huggingface dataset:
AB0393 Comparison of multi-line dot assay and enzyme-linked immunosorbent assay for detection of autoantibody profile in antiphospholipid syndrome
Authors: E. Alexandrova, T. M. Reshetnyak, N. V. Seredavkina, Z. G. Verizhnikova, A. A. Novikov, D. Roggenbuck, E. L. Nasonov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Diagnosis of antiphospholipid syndrome (APS) still remains a laboratory challenge due to the great diversity of antiphospholipid antibodies (aPL) and their significance regarding APS classification criteria. Standardized enzyme-linked immunosorbent assay (ELISA) for antibodies to cardiolipin (aCL) and b2-glycoprotein I (ab2GPI) has been indispensable in the diagnosis and management of APS. Multiplex detection of aPL profile seems to be a new approach for risk assessment in APS. <h3>Objectives</h3> The comparison of the novel multi-line dot assay (MLDA) with results of the routine ELISA technique for detection of aPL in APS. <h3>Methods</h3> We studied 36 patients (pts) with APS (5 men, 31 women, median age 34, 29-44 years). Diagnosis of APS had been established according to the 2006 international classification criteria. 15 (41,7%) APS pts met the diagnostic criteria for systemic lupus erythematosus (SLE), 28 (77,8%) had a history of arterial and/or venous thrombosis, 21 (58,3%) suffered from fetal loss. As a disease control group, 14 pts with SLE without APS (3 men, 11 women, median age 35, 27-45 years) were included. IgG/IgM antibodies to CL, b2GPI, phosphatidylserine (aPS) and phosphatidylinositol (aPI) in the pts sera were detected using a commercial available MLDA ("Medipan", Germany). For comparison, the serum levels of IgG/IgM aCL and ab2GPI were measured by ELISA kit ("Orgentec", Germany). <h3>Results</h3> APS pts demonstrated a significantly higher frequency of IgG aCL, IgG and IgM ab2GPI in ELISA and IgG aCL in MLDA compared to SLE pts (p&lt;0,05) (table 1). The agreement between both methods was good for IgG aCL, IgM aCL and fair for IgG ab2GPI, IgM ab2GPI (kappa=0,620, 0,628, 0,380 and 0,388, respectively). The frequency of discrepant results for IgG aCL, IgM aCL, IgG/ IgM ab2GPI was 16%, 18% and 30%. Multiple positivity for different aPL detected by ELISA occurred significantly more frequently in APS pts (27,8%) in contrast to SLE pts (7,1%, p&lt;0,05). The number of multiple positive samples evaluated by MLDA in the APS group (13,9%) did not demonstrated a significant higher prevalence in comparison with the control group (7,1%, p&gt;0,05). There was a relationship between ischemic stroke and the combination of high positive levels of IgG/IgM aCL, ab2GPI, aPS and aPI detected by MLDA in APS pts (OR 95%CI 2,45, 1,09-5,55, ρ=0,049). We didn't find any associations between subtypes of aPL and thrombosis localization. <h3>Image/graph</h3> <h3>Conclusions</h3> MDLA present an alternative to ELISA for aPL evaluation and profiling in APS. The rate of false-positive aPL detected by MLDA in SLE pts was higher compared to ELISA. The combination of four high positive aPL measured by MLDA is a risk factor of ischemic stroke in APS. <h3>Disclosure of Interest</h3> None Declared
Abstract 4547: High-throughput screen to identify compounds targeted to embryonal rhabdomyosarcoma harboring mutant HRAS using cells derived from a pediatric Costello syndrome patient.
Authors: Donna M. Cartledge, Katherine M. Drake, Karen W. Gripp, Katia Sol-Church, E. Anders Kolb, Andrew D. Napper
Journal: Cancer Research (2013)

Abstract Costello syndrome (CS) is a disorder caused by HRAS gene mutations. Substitutions in glycine residues at positions 12 or 13 of the HRAS gene lead to aberrant activation of the guanine-nucleotide binding protein, HRAS. Homozygous expression of mutant HRAS predisposes pediatric patients to early onset of cancer, especially embryonal rhabdomyosarcoma (ERMS), while heterozygosity at this locus results in non-malignant abnormalities. Since the mid 1970’s there has been only a modest increase in the 5-year survival rate for ERMS in the United States to no more than 70%, so new treatment strategies are needed. To address this need, we have acquired, propagated, and banked patient-derived ERMS cells harboring a homozygous p.G12A substitution and have used these cells to develop a high-throughput screening (HTS) assay to discover compounds that selectively kill cells bearing homozygous HRAS mutation. The assay employs luminescent detection of ATP using CellTiter-Glo to quantify cell viability. Cell number, growth conditions, and compound delivery were optimized to obtain a robust 72-hr cell growth assay. The potent cytotoxic agent dactinomycin was used to ensure reproducible sensitivity of the assay. The assay was validated for HTS by pilot screening of a library of 2,000 known drugs and bioactive natural products, and hits were confirmed by retesting in dose-response. Confirmed active compounds were tested for selectivity for ERMS harboring homozygous mutant HRAS in a panel of patient-derived and purchased cell lines: RD, an ERMS line not driven by HRAS mutation; RH36, a mutant HRAS (p.Q61K) ERMS line that is not derived from CS; fibroblasts derived from CS patients with heterozygous HRAS mutations (CS242, p.G12A and CS066, p.G12S), and normal fibroblasts. In future work, compounds identified by HTS as displaying selectivity for homozygous mutant HRAS-expressing ERMS cells will be evaluated in pairwise combinations and also in combination with currently used chemotherapeutics. Targeting mutant HRAS-activated cell growth could direct the design of a novel therapeutic strategy for treatment of children with ERMS. Citation Format: Donna M. Cartledge, Katherine M. Drake, Karen W. Gripp, Katia Sol-Church, E. Anders Kolb, Andrew D. Napper. High-throughput screen to identify compounds targeted to embryonal rhabdomyosarcoma harboring mutant HRAS using cells derived from a pediatric Costello syndrome patient. [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 4547. doi:10.1158/1538-7445.AM2013-4547
AB1148-HPR A Factual Survey on Pregnancy and Delivery in Rheumatoid Arthritis Patients -The Role of Nurses as Suggested by Patient Questionnaire Surveys-
Authors: M. Kaneko, S. Honjo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) tends to have its onset in women in their 40s or 50s, and not a few of these patients are still of childbearing potential. It used to be necessary to forgo pregnancy and delivery because of RA treatment, but with rapid advances in treatment drugs for RA, we have entered an era in which RA patients can become pregnant and deliver. <h3>Objectives</h3> We conducted a survey to investigate actual conditions among RA patients who have experienced pregnancy and delivery, to consider the role of nurses in their treatment. <h3>Methods</h3> Since biologics became available for RA treatment in Japan in 2003, our clinic has conducted interview-style questionnaire surveys of RA patients who have experienced pregnancy and delivery. <h3>Results</h3> Seven of RA patients had experienced delivery. Two of the 7 RA patients had experienced delivery 2 times. and in all cases, both mother and child were normal. We now have 2 patients who are newly pregnant. The specific sources of anxiety concerning pregnancy and delivery included that the effects of RA treatment drugs on the fetus, the postpartum condition, advisability of use of RA treatment drugs while nursing, and effects of RA treatment drug while nursing on the newborn. On the other hand, they feel that they have sufficient understanding and cooperation from family members with respect to their pharmacotherapy during pregnancy and delivery. Before becoming pregnant, 5 of these patients had used etanercept (ETN), 1 had used infliximab, and 1 had used a steroid, and although 2 went drug-free after becoming pregnant, the other 5 continued to use the same treatment drugs they had used before becoming pregnant. All of the patients fed their babies with a combination of mother9s milk and artificial milk, and 3 of them continued ETN monotherapy during the period of lactation. <h3>Conclusions</h3> This survey elucidated the concerns of RA patients with respect to pregnancy and delivery. It shows the importance of having nurses address not only care of the disease itself but also total management entailing the building of relationships of trust with patients of reproductive age early on while providing mental care that includes the families, collaborating with departments of obstetrics, and collecting information, etc. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2804
Tales of crack: Some quotes from patients and their doctors
Authors: S. Cembrowicz
Journal: BMJ (1999)

Crack cocaine, also known as freebase or Charlie, is a compound of cocaine which is smoked, giving rapid absorption via the lungs and a brief “rush” of euphoria, with feelings of invincibility. It inhibits monoamine reuptake by binding to dopamine, noradrenaline, and serotonin system membrane transporters. Its half life is 50 minutes, and dysphoria—possibly caused by dopamine depletion—may rapidly follow. Twenty per cent of experimenters are said to become regular users. A small “rock” of crack can cost a few pounds. Crack has become widely available on thedrug scene in the past 10years. Its use is said to be linked with violent crime and prostitution. Some users start on opiates to deal with dysphoria related to crack.

No substitution treatment is available, but dopamine reuptake blockers such as desipramine are being investigated.

“I used to take up to £4500 worth in one week. I …
PERFORIN-POSITIVE CARDIAC CELL INFILTRATION AND MALE GENDER PREDICT ADVERSE LONG-TERM MORTALITY IN INFLAMMATORY CARDIOMYOPATHY
Authors: Felicitas Escher, Uwe Kuehl, Dirk Lassner, Burkert Pieske, Wolfgang Poller, Carsten Tschoepe, Heinz-Peter Schultheiss
Journal: Journal of the American College of Cardiology (2016)
SAT0493 The Relation of Age, Bone Microarhitecture Index (TBS), and Bone Mineral Density (BMD) in Healthy Women in Menopause
Authors: S. Novkovic, G. Marinkovic, S. Prodanovic, M. Panic, M. Terek
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To assess the relationship between age, the value of TBS and BMD in healthy postmenopausal women. <h3>Methods</h3> In a cross sectional study including 257 healthy menopausal women, who underwent osteodensitometric (DXA) examination of the lumbar (L) spine and hip, with TBS score the L spine measured. The survey excluded all subjects with risk factors that could affect bone microarchitecture (steroids, previous fractures, systemic disease, excessive use of alcohol and cigarettes, as well as the use of drugs with a negative impact on bone metabolism). Statistical analysis was performed in SPSS system, appropriate statistical methods. <h3>Results</h3> The average age of patients was 64.3±7.9 years. The average value of L spine BMD was 0.859±0.153 g/cm<sup>2</sup>, while average hip BMD was 0.795±0.123 g/cm<sup>2</sup>. The mean value of TBS was 1.223±0.101. There was a significant positive correlation between the TBS and L spine BMD (r =0.487, p&lt;0.001) and between the TBS and the hip BMD (r =0.292, p&lt;0.001). A significant negative correlation was observed between age and TBS (ρ = -0.218, p&lt;0.001), as well as the age and the BMD of the hip (ρ = -0.201, p&lt;0.001), while the age and L spine BMD were not significantly correlated (ρ = -0.003, p=0.959). <h3>Conclusions</h3> Any change in bone mineral density of the L spine and hip causes a change in the index of bone microarchitecture in the same direction. A reduction in the value of the bone microarchitecture index and bone mineral density of the hip is connected with aging. There was no significant variation in bone mineral density at L spine with age, which may indicate the progression of degenerative changes of the spine. TBS is an independent parameter, which has the potential diagnostic value itself, not taking into account the BMD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2996
Abeloff Ends ASCO Tour; Assesses Issues Faced
Authors: J. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Abeloff Ends ASCO Tour; Assesses Issues Faced Get access Jan Ziegler Jan Ziegler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 10, 20 May 1992, Pages 750–751, https://doi.org/10.1093/jnci/84.10.750 Published: 20 May 1992
SERIAL MEASUREMENT OF TUMOR NECROSIS FACTOR-α, INTERLEUKIN-6 AND VASCULAR ENDOTHELIAL GROWTH FACTOR AS A FUNCTION OF CACHEXIA IN PATIENTS WITH CHRONIC HEART FAILURE: RESULTS FROM THE PROBNP OUTPATIENT TAILORED CHRONIC HEART FAILURE (PROTECT) STUDY
Authors: Arianna Belcher, Parul Gandhi, James Januzzi, Hanna Gaggin
Journal: Journal of the American College of Cardiology (2015)
PWE-134 Single incision vs conventional laparoscopic cholecystectomy: a meta-analysis and systematic review of randomised controlled trials
Authors: M Sajid, N Ladwa, M K Baig, K Singh, M Sayegh
Journal: Gut (2012)

<h3>Introduction</h3> To systematically analyse the randomised trials comparing single incision laparoscopic cholecystectomy (SILC) vs conventional laparoscopic cholecystectomy (CLC). <h3>Methods</h3> The meta-analysis was conducted according to the Quality of Reporting of Meta-analysis (QUORUM) standards. Standard electronic databases were searched to retrieve relevant randomised trials comparing SILC vs CLC and analysed systematically using RevMan®. Summated outcomes were expressed as RR and standardised mean difference (SMD). <h3>Results</h3> Eleven randomised, controlled trials encompassing 859 patients were retrieved for the electronic databases. In the random effects model, post-operative pain, post-operative complications, length of hospital stay, cosmesis score, conversion rate, additional ports insertion rate and time for return to normal activities were statistically comparable between two techniques of cholecystectomy. The SILC is associated with longer operative time. However, there was significant heterogeneity among included trials. <h3>Conclusion</h3> SILC does not offer any significant advantage over CLC to treat benign gallbladder disorders. CLC may assiduously be used for this purpose. <h3>Competing interests</h3> None declared.
Abstract 769: Effect of cucurbitacin B, a medicinal herb extract from <i>Trichosanthes cucumerina,</i> on Wnt signaling pathway in breast cancer cells
Authors: Sumana Dakeng, Suwit Duangmano, Weena Jiratchariyakul, Oliver Bögler, Pimpicha Patmasiriwat
Journal: Cancer Research (2010)

Abstract The cucurbitacins are tetracyclic triterpenes found in plants of the family Cucurbitaceae. Cucurbitacins have been shown to have anticancer and anti-inflamatory activities. In this study, we investigated the anticancer activity of cucurbitacin B and dihydrocucurbitacin B extracted from Thai medicinal plant Trichosanthes cucumerina. A mixture compound of cucurbitacin extracts containing cucurbititacin B and dihydrocucurbitacin B in an 8:1 molar ratio was dissolved in 10% dimethylsulfoxide and diluted with DMEM to the desired concentrations prior to use. Cell viability was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results indicated that mixture of cucurbitacin B (mixture CuB) from T. cucumerina have cytotoxic effect on breast cancer cell lines, SKBR-3, MCF-7, HBL-100 and T47D with the IC50 of 4.60 µg/ml, 88.75 µg/ml, 55.46 µg/ml and &amp;gt;100 µg/ml respectively. Flow cytometry for cell cycle analysis was performed after treated cells with mixture CuB. We found that growth inhibition effect was attributed at G2/M phase arrest and apoptosis. Western blotting analysis showed increase PARP cleavage and decrease Wnt associated signaling molecules including β-catenin, galectin-3, cyclin D1 and c-Myc. We also found that mixture CuB inhibit nuclear-translocation of β-catenin and galectin-3 when compared with vehicle control cells. The depletion of β-catenin and galectin-3 in the nuclease was confirmed by cellular protein fractionation method. TCF promoter, a downstream signaling of Wnt was also disrupted in cucurbitacin B treated cells. TCF promoter assay system was used for assessment of TCF promoter activity. The relative luciferase activity was reduced when we treated cells with mixture CuB for 24 hours. Our data indicate that cucurbitacin B and their derivative dihydrocucurbitacin B from T. cucumerina induce apoptotic cell death and exhibit growth inhibitory effect via inhibition of Wnt signaling pathway. 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 769.
Oncogene Meeting Focuses On Regulatory Pathways
Authors: P. A. Newman
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Oncogene Meeting Focuses On Regulatory Pathways Get access Patricia A. Newman Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 18, 20 September 1989, Pages 1349–1351, https://doi.org/10.1093/jnci/81.18.1349 Published: 20 September 1989
Abstract 2878: A sensitive cell signaling assay for low level activation of endogenous receptors – a comparison of AlphaScreen® SureFire® and TR-FRET assays
Authors: Stephen Hurt, David Titus
Journal: Cancer Research (2011)

Abstract Two closely related proteins, ERK1 and ERK2, belong to a widely conserved family of serine/threonine protein kinases whose activities are regulated by phosphorylation. These kinases are components of signal transduction pathways which control critical cellular processes such as growth, differentiation, metabolism and apoptosis. In addition to normal cellular processes, these pathways have been associated with signaling in many cancers. Phosphorylation of ERK 1/2 has been shown to be mediated by signal transduction pathways which are activated by ligand binding to both receptor tyrosine kinase receptors (RTKs) and G protein-coupled receptors (GPCRs). The focus of cell signaling studies is increasingly shifting to endogenous cell surface receptors rather than recombinant, over-expressed receptors. The hope is that these model systems will have greater biological relevance, more closely reflecting the physiology of the organism studied. In such studies the sensitivity of the assay platform becomes critical for success, especially when the endogenous receptors are activated at low levels. Several technologies have been used to quantitate relative levels of protein phosphorylation, including western blot, time-resolved fluorescence resonance energy transfer (TR-FRET), and AlphaScreen® SureFire® assays. AlphaScreen® SureFire® assays are homogenous, bead-based assays designed to measure endogenous levels of intracellular phosphorylated proteins. Here we describe the performance of the AlphaScreen® SureFire® p-ERK 1/2 assay compared to that of a TR-FRET assay. For this study we used two different cell lines. The first was CHO-K1 cells stably transfected with the human somatostatin sst5 GPCR, which is stimulated by its natural ligand somatostatin-28. The second was wild-type HEK 293 cells, which express endogenous receptors for epidermal growth factor (an RTK), and endogenous GPCRs activated by acetylcholine and ATP. In general, the AlphaScreen® SureFire® assay gave higher S/B ratios than the TR-FRET assay in all conditions tested, which in turn can have a significant impact on the assay robustness. In situations that gave wide response windows, such as stimulation of the CHO over-expressed somatostatin receptor or the HEK 293 endogenous EGF receptor, both assay kits yielded excellent results. However, the HEK 293 endogenous GPCRs for acetylcholine and ATP are coupled to a lower production of p-ERK, and in those cases the AlphaScreen® SureFire® assay proved to be much more robust, with significantly higher overall signal levels and S/B ratios. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2878. doi:10.1158/1538-7445.AM2011-2878
Abstract C9: Quantitative modeling of androgen receptor-mediated transcriptional complexes in human prostate cancer cells
Authors: Jordy J. Hsiao, Hairyl D. Martinez, Michael E. Wright
Journal: Cancer Research (2011)

Abstract The androgen receptor (AR) is a member of the nuclear receptor superfamily and the key transcription factor of androgen-mediated signaling pathways. AR translocates to the nucleus in response to ligand binding, where it selectively binds canonical androgen response elements (AREs) in DNA to assemble transcriptional complexes at target genes. Aberrant AR signaling resulting from unbalanced AR transcriptional responses at genes involved in cellular proliferation and differentiation drives the development and progression of human prostate cancers. In addition, the AR coregulator proteins, members of a large family that bind AR and modulate AR transcriptional activity, are known to elicit aberrant AR activity in prostate cancers. Although numerous AR coregulators have been identified, in most cases this was through static, binary protein-protein interaction assays (e.g., GST-fusion, yeast two-hybrid assays). Thus, to what degree androgen-sensitive coregulators mediate pathological AR actions in the context of human prostate cancer remains poorly defined. We have devised a biochemical strategy to identify and quantify androgen-sensitive coregulators (coactivators and corepressors) of AR-mediated transcription, based on their in vitro affinity for a model androgen-regulated gene promoter. Specifically, we have used DNA-affinity purification techniques in combination with label-free quantitative mass spectrometry (qMS) to do so. Our preliminary findings show that androgen-sensitive coregulators represent a functionally diverse group of protein involved in a number of signal transduction pathways. Furthermore, future studies utilizing selected reaction monitoring (SRM), a quantitative proteomics method, will be exploited to study the molecular functions of androgen-sensitive coregulators and facilitate the construction of quantitative models of AR-mediated transcription that will make it possible to predict androgenic responses at disease-associated, androgen-regulated genes. Our findings will broadly benefit the biomedical research community in that they define a novel class of androgen-sensitive coregulators and determine how they influence AR-mediated transcriptional processes underlying the development and progression of human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C9.