tbuckley/cabot-search huggingface dataset:
Abstract 1000: ATP7A mutation reduces resistance to chemotherapy agents <i>in vitro</i> and <i>in vivo</i>.
Authors: Sha Zhu, Michael J. Petris
Journal: Cancer Research (2013)

Abstract The Menkes protein (ATP7A), a copper-translocating P-type ATPase, is responsible for the loading of copper from the cytosol into secretory compartments of the cell for incorporation into newly synthesized copper-requiring enzymes. Previous studies using cultured cell lines have suggest that ATP7A is able to modulate cellular accumulation of cisplatin, a platinum-containing chemotherapy agent. In this study, we generate isogenic ATP7A-WT and ATP7A-knockout mouse embryonic fibroblast cells line pairs. We demonstrate that ATP7A deletion significantly decreases cellular resistance to cell cycle non-specific platinum agents, cisplatin &amp; carboplatin and cell cycle specific alkaloid agent, vincristine sulfate. In addition, loss of ATP7A sensitizes xenograft tumor growth to cisplatin toxicity. These findings identify the ATP7A copper transporter as an active participant in multidrug resistance pathways in vivo, underscoring this transporter as a potential drug target to augment platinum-based chemotherapeutics. Citation Format: Sha Zhu, Michael J. Petris. ATP7A mutation reduces resistance to chemotherapy agents in vitro and in vivo. [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 1000. doi:10.1158/1538-7445.AM2013-1000
FRI0019 Peripheral blood neutrophils derived from patients with rheumatoid arthritis exhibit increased neutrophil extracellular trap formation
Authors: G. Papadaki, C. Choulaki, I. Mitroulis, P. Verginis, A. Repa, A. Raptopoulou, D. Boumpas, P. Sidiropoulos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Neutrophils are the most abundant cell type identified in the joints from patients with rheumatoid arthritis (RA), with a key role in inflammation and cartilage damage. Activated neutrophils form extracellular traps (NETs), with potent pro-inflammatory and immunostimulatory activity. <h3>Objectives</h3> We sought to assess the role of NET release in RA pathogenesis. <h3>Methods</h3> Peripheral blood neutrophils from active RA patients (n=6) (Disease activity score, DAS28 &gt;5.1) and control subjects (n=7) were isolated. NET formation from RA neutrophils (peripheral blood/synovial fluid-derived) and control neutrophils treated with RA serum (n=7) or synovial fluid (n=7) was assessed by immunofluoresence microscopy, using co-staining with myeloperoxidase and 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI). The percentage of NET releasing cells was determined by examining 200 cells per sample in a double blind fashion. Time course experiments revealed optimal NET release at 3 hours. <h3>Results</h3> Freshly isolated RA neutrophils from peripheral blood underwent spontaneous NET release at higher rates compared to normal controls (12±2.1% vs 3.21±0.9%, p&lt;0.05). Interestingly, neutrophils derived from RA synovial fluid exhibited even higher rates of NETosis. Treatment of control neutrophils with either RA serum or RA synovial fluid increased NET release compared to cells treated with normal serum (16±2.5% or 9±1.5%, vs 3.2±0.7 p&lt;0.005). Inhibition studies in progress address the impact of inflammatory cytokines and/or immune complexes in NET production, as well as the impact of NETs on dendritic and T cell activation. <h3>Conclusions</h3> Neutrophil activation in RA is associated with enhanced NET formation, driven by soluble factors found in RA sera and synovial fluid. Whether NETs are involved in the cross-talk between neutrophils and adaptive immune responses in RA is under investigation. <h3>Disclosure of Interest</h3> None Declared
AB0373 Interrelation of level pro-hepcidin with development of an anemia in patients with rheumatoid arthritis
Authors: D. Belenkiy, E. Galushko, A.A. Novicov
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The leading pathogenetic factor in development of the anemia of chronic disease is disturbance of the exchange of iron. Pro-hepcidin, a recently indentified peptide, acts as a central regulating the uptake of dietary iron and its mobilization from macrophages and hepatic stores. It is considered as a mediator of anemia of inflammation. <h3>Objectives</h3> to estimate interrelation of level Pro-hepcidin with indicators of activity of inflammatory process and hemoglobin level (Hb) at patients with (RA). <h3>Methods</h3> It has been included 76 patients with RA average- 46,3 years, duration of desease 60[17;96] month, activity on DAS 28- 6,15±1,35. The anemia has been diagnosed for 47 patients by criteria the CART (Hb 104,3±21,4 g/l. Concentration of serum pro-hepcidin in blood defined an immunoenzymatic method.Serum iron defined with the help a method with use of an ascorbate and ferrosin as a reagent, Serum firms Roche Integra Gen.2 Ferritin defined with the help immunology, a method based on agglutination of a ferritin with latex particles, the covered antibodies to a ferritin. <h3>Results</h3> It has been included 76 patients with RA (65 women and 11 men), compare age - 46,3 years, duration of disease 60 [17; 96] month, activity on DAS28 –(6,15±1,35 points).The anemia has been diagnosed for 47 patients by criteria the CART (Hb 104,3±21,4 g/l).Patients with anemia (N=47) and with out (N=29) were comparable (p&gt;0,05) on age 45,5±14,3 and 48,9±14,3 years, duration of illness 60 [36; 96] and 60 [17; 84] month, DAS28-6,4±1,7 and 5,9±1,0 levels of CRP (44,5[20,3; 110,2] and 37,8[12,7; 47,2] mg/l) ESR (46,5±21,3 and 41,0±20,3 mm/h). Serumal iron was much more low at patients with the anemia (9,5±5,6 and 18,5±7,7 mkmol/l, p=0,01).The Pro-hepcidin level was higher at patients with RA and with the anemia, than with out it (120,3±56,1comparison with 90,3±37,9ng/ml, p=0,04).In group with the anemia direct correlation between hemoglobin level, Pro-hepcidin and (r=0,45; p=0,01) in the ferritin (r=0,52; p=0,002). Has been taped Pro-hepcidin also correlated with serumal iron, levels DAS28. In group of patients with normal concentration of hemoglobin Pro-hepcidin positively correlated with indicators of activity of inflammatory process CRP, ESR DAS28 (rCPR=0,51, p=0,03; rESR=0,62, p=0,01; rDAS28=0,4; p=0,025) interrelations levels of hemoglobin and serum iron were not. <h3>Conclusions</h3> At patients with Rheumatoid arthritis (RA) rising of level serum Pro-hepcidin in blood is bound not only to activity of inflammatory process, but also is independent predictor of developments ACD. <h3>Disclosure of Interest</h3> None Declared
Shaken baby expert must disclose fitness to practise charges when asked to give evidence in new cases
Authors: C. Dyer
Journal: BMJ (2015)

A leading UK neuropathologist and expert witness in shaken baby cases must tell anyone who commissions her to prepare an expert report that she is facing fitness to practise charges, under conditions imposed on her medical registration.

The decision to impose interim conditions on Waney Squier’s registration was made by the Medical Practitioners Tribunal Service after the disclosure that she failed to mention her upcoming hearing when agreeing in April 2014 to …
Abstract LB-388: Regulation of histone deacethylase 8 expression by inhibitory GTP binding proteins in H1299 non-small-cell lung cancer cells
Authors: Hwa-jeong Hahn, Yong-sung juhnn
Journal: Cancer Research (2012)

Abstract Histone deacetylases (HDACs) have been reported to regulate the cell growth, cell proliferation, cell cycle, and apoptosis, and increased expression of HDAC (classI) was observed in many kinds of cancer. HDAC8, most recently discovered subtype of HDAC classI, seems to be involved in tumor growth and progression because it is highly expressed in several cell lines and human cancer tissues. Inhibitory heterotrimeric GTP-binding proteins (Gi) are activated by seven transmembrane receptors bound with ligands, and regulate cellular metabolism and proliferation by regulating the activity of adenylate cyclase, activate phospholipase C beta, and ion channels. Thus, we made a hypothesis that Gi signaling system may regulate the expression of HDAC8, and this study investigated the effects of Gi signaling system on the expression of HDAC8 and the underlying mechanism in lung cancer cells. When Gi signaling system was activated by expressing Gαi1Q204L, a constitutively active mutant Gαi1, the expression of both HDAC8 protein and mRNA was increased in H1299 non-small-cell lung cancer (NSCLC) cells. However, the HDAC8 promoter activity did not increased significantly, and treatment with Actinomycin D did not block the increase in mRNA. The degradation of HDAC8 mRNA was facilitated in Gαi1Q204L-expressing cells, indicating Gi signaling system increases HDAC8 expression by stabilizing mRNA. Furthermore, treatment with adenosine or CCPA (2-chloro-N(6)cyclopentyladenosine), which bind to adenosine receptors leading to Gαi1 activation, also increased both HDAC8 mRNA and protein levels in H1299 cells. The effect of adenosine was blocked by treatment with DPCPX (8-Cyclopentyl-1,3-dipropylxanthine), an adenosine A1 receptor antagonist. These results indicate that Gi signaling system increases the HDAC8 expression by stabilizing its mRNA in H1299 NSCLC cells Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-388. doi:1538-7445.AM2012-LB-388
AB0339 Role of cholesterol ester transfer protein in inflammation mediated dyslipidemia of rheumatoid arthritis patients
Authors: V. Hernandez-Hernandez, I. Ferraz-Amaro, E. Delgado-Frías, M. Flores-Rodríguez, J. Viotti, C. Rodríguez de la Rosa, M. Gantes, M. Dominguez-Luis, A. Herrera-García, A. Rodríguez-Vargas, F. Diaz-Gonzalez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Rheumatoid Arthritis (RA) patients show alterations in cholesterol and lypoproteins levels. These disturbances seem to be related to the inflammation that takes place in the disease, but the pathological mechanisms that leed to it are unknown. Cholesterol ester transfer protein (CETP) is an enzyme that allows transference of cholesterol ester from HDL to LDL-cholesterol particles. CETP has recently gained interest as therapeutic goal of new treatments developed to treat dyslipidemia. The aim of this study is to describe the role of this enzyme in a model of chronic inflammation associated dyslipidemia as it occurs in rheumatoid arthritis. <h3>Methods</h3> 101 RA patients and 115 sex and age-matched controls were included. Serum levels of CEPT were measured by an enzimelinked inmunoassay and the enzymatic activity by a specific kit (Roar CEPT activity assay kit). In both patients and controls classical lipidic profile (cholesterol, triglycerides, HDL and LDL cholesterol, apolipoprotein A1, apolipoprotein B and lipoprotein A) was defined. Also ESR and CRP were determined. In RA patients disease activity indexes like DAS28 and HAQ were collected, as well as, sociodemographic variables, comorbidility and anthropometric variables. Multivariate analysis was performed to compare results between patients and controls adjusting for corticosteroids intake and for classical dyslipidemia risk factors. <h3>Results</h3> Serum protein levels were correlated with the enzimatic activity (r=0,5, p=0,00), showing that serum levels could be enough to express the activity of this enzime. Patients show lower CETP activity levels after adjusting for sex and age (beta coefficient -0,52 pmol/l, CI95% -0,87–0,18, p=0,01). In patients, CRP levels show a negative correlation with CETP activity (r=-0.34, p=0,03); in controls this correlation did not achieve the stadistic significance. Disease activity scores like DAS28 did not show association with CETP. <h3>Conclusions</h3> CETP is underexpressed in RA patients. Differencial characteristics of dyslipIdemia in RA could be partly explained by this fact. <h3>Disclosure of Interest</h3> None Declared
ROLLING OUT ECCO GUIDELINES FOR OPPORTUNISTIC INFECTIONS INTO DAY TO DAY PRACTISE-STILL A WAY TO GO!!!
Authors: L M Jackson, W A Stack, J McCarthy, U Lannin, J O Keefe
Journal: Gut (2013)

<h3>Introduction</h3> Best practise guidelines recommend that all patients starting Anti-TNF therapies should be pre-screened and vaccinated to reduce risk of opportunistic infections (ECCO guidelines 2009) and should be counselled re potential risks and benefits of treatments. <h3>Aims/Background</h3> To review documentation of anti-TNF therapy information provision and compliance with ECCO guidelines in prevention of opportunistic infections. <h3>Method</h3> We reviewed retrospectively the notes of all patients receiving infliximab therapy between Sep 2009 and Sep 2012 in BSH GI unit, Cork. <h3>Results</h3> 327 no of infusions was given to 39 patients (16 crohns/23 UC, M:F ratio 21:18) over study period. Discussion re treatment risks was clearly documented in 32/37(86%) patients, in 84% cases by IBD specialist nurse. Screening for opportunistic infections was incomplete. TB screening was undertaken in 100% (37/37) of cases but HIV testing was not routinely undertaken. 65%(24/37) patients had Hep B immunity status assessed but none were referred for vaccination programme. Varicella immunity was checked in 46% (17/37) patients, 2/17 (11.8%) patients non-immune! New tick-box proforma designed. <h3>Conclusion</h3> Rolling out of new guidelines which encorporate new practise is challenging and difficult to coordinate. In an effort to standardise approach we have designed a tick box proforma to use as part of our initial assessment of IBD patients. Our aim is to screen all patients at point of diagnosis of illness rather than at point of prescribing therapy so that vaccination can be coordinated when necessary in anticipation of requirement of therapies. Further studies will be required to look at success of this measure.
Combination of Initial Stimulation Thyroglobulins and Staging System by Revised ATA Guidelines Can Elaborately Discriminate Prognosis of Patients With Differentiated Thyroid Carcinoma After High-Dose Remnant Ablation
Authors: Min-Hee Kim, Sun Hee Ko, Ja-Seong Bae, Dong-Jun Lim, Ki-Hyun Baek, Jong-Min Lee, Moo-Il Kang, Bong-Yun Cha
Journal: Clinical Nuclear Medicine (2012)

Purpose The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6–12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. Patients and Methods Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2–10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. Results A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. Conclusion Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.
Exploiting Glutamine Addiction of Tumor Cells for Selective and Improved Delivery of Chemotherapic Drugs in Cancer Treatment
Authors: M.D.S. Neto, S.P. Ramos, R. Curvello, M. Bin, N.L.C. Domingues, A.W. Rinaldi, A. C. Santos de Souza
Journal: Annals of Oncology (2013)
18F-FDG PET Imaging in a Patient With Late Omental Infarction After Treatment of Pancreatic Adenocarcinoma
Authors: Guillaume Chassagnon, Gilles Metrard, Hélène Besse, Sabine Gauvain
Journal: Clinical Nuclear Medicine (2014)

We report a case of late omental infarction visualized by F-FDG PET/CT during follow-up for pancreatic adenocarcinoma. The 65-year-old patient was referred for imaging 8 months after pancreaticoduodenectomy and 2 months after completion of a course of chemotherapy. PET/CT showed an FDG-avid omental lesion that suggested peritoneal carcinomatosis. The appearance and evolution at follow-up studies confirmed the diagnosis of omental infarction, a rare complication of pancreatic surgery. This case revealed the possibility of late FDG uptake in omental infarction.
Abstract 4864: Antibody detection of translocations (ADOT) in Ewing's sarcoma
Authors: Wen Luo, Brett Milash, Brian Dalley, Richard Smith, Natalie Dutrow, Brad Cairns, Stephen Lessnick
Journal: Cancer Research (2011)

Abstract Objective: The detection and identification of chromosomal translocations has important implications in the diagnosis, prognosis, and treatment of patients with cancer. Current approaches to translocation detection often have significant shortcomings, including limited sensitivity and/or specificity, and can be difficult to apply to formalin-fixed paraffin-embedded (FFPE) clinical samples. We developed a new approach, antibody detection of translocations (ADOT), that avoids many of the shortcomings of current techniques. Methods: ADOT combines a transcriptional microarray-based approach with a novel antibody-based detection method. Microarrays were designed that probe for every possible fusion transcript in Ewing's sarcoma, both previously identified and theoretical. These include EWS/FLI, EWS/ERG, EWS/ETV1, EWS/ETV4, EWS/FEV and others. Total RNA, purified from Ewing's sarcoma cells or tumors (that express different types of translocations), is hybridized to the custom microarrays. A high-affinity antibody (S9.6) that binds to RNA-DNA duplexes formed during hybridization is used as a detection reagent. Results: We demonstrate the feasibility of ADOT by examples in which both known, and unknown, translocation fusion transcripts are identified from cell lines, tumor xenografts, and primary tumor samples. Translocation fusion points identified by ADOT were confirmed using traditional RT-PCR and sequencing. Furthermore, ADOT is able to detect translocations in FFPE tumor samples in which case RT-PCR fails. The sensitivity of ADOT to detection of translocations is also determined. Conclusion: ADOT allows for the accurate and sensitive identification of translocations and also provides exon-level information about the specific fusion transcript produced. Furthermore, the technique is readily generalizable to any potential fusion transcript, and can also detect previously undescribed fusions. This suggests that ADOT may be used as a diagnostic tool for pediatric sarcoma or other translocation-based cancers. 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 4864. doi:10.1158/1538-7445.AM2011-4864
Pancreatic pseudocyst with complicating colonic fistula successfully closed using the over-the-scope-clip system
Authors: Yuta Koike, Takahiko Kudo, Taku Shigesawa, Yomo Fujita, Ayana Endo, Yuji Ono, Michio Nakamura, Atsushi Nagasaka, Shuji Nishikawa
Journal: Endoscopy (2014)

A 53-year-old man had a history of alcohol-induced chronic pancreatitis. In July 2011, because of suspicion of a pseudocyst infection, he had undergone endoscopic ultrasound (EUS)-guided cyst drainage. Further investigation after drainage had revealed a fistula between the pancreatic pseudocyst and descending colon; however, the transgastric internal drainage tube was left in place because of the severity of the patient's condition.
Junior doctors’ dispute: a pollster’s view
Authors: Ben Page
Journal: BMJ (2016)

Ben Page assesses what the polls tell us about the public’s view of strike action

Doctors don’t normally strike. They have been the most trusted profession in the United Kingdom ever since we first asked about the veracity of different professions in the 1980s. The clergy has seen its levels of trust fall, and that of scientists has risen, but, year in year out, nothing has blunted the public’s trust in doctors. Not even Harold Shipman. In contrast fewer than one in four people trust cabinet ministers to tell the truth, and the Department of Health was always going to be on the defensive. So when the BMA announced strike action, I expected public support to be high. Since January 2016 we have measured public …
F-18 Fluorodeoxyglucose Positron Emission Tomography in Mesenterial Castleman’s Lymphoma
Authors: SATOSHI KUNISHIMA, HIROKI TANIGUCHI, TOSHIMORI KOH, AKIHIRO YAMAGUCHI, HISAKAZU YAMAGISHI
Journal: Clinical Nuclear Medicine (2001)

KUNISHIMA, SATOSHI M.D.; TANIGUCHI, HIROKI M.D.; KOH, TOSHIMORI M.D.; YAMAGUCHI, AKIHIRO M.D.; YAMAGISHI, HISAKAZU M.D. Author Information