tbuckley/cabot-search huggingface dataset:
Abstract A43: Inhibition studies of Siah2, a ubiquitin ligase, involved in hypoxia induced cancer
Authors: Anupriya Gopalsamy
Journal: Cancer Research (2011)

Abstract Ubiquitin ligase siah2 has been shown to regulate the hypoxia response by regulating prolyl hydroxylase3 (PHD3) involved in a hypoxia inducible factor 1α (Hif-1α) dependent pathway which up regulates the genes like vascular endothelial growth factor (VEGF), resulting in tumor cell survival. Thus it has been suggested that siah2 may act as a target for developing inhibitors. In this study we have proved the interaction of siah2 and PHD3 using co-immunoprecipitation and GST pull down assay. Interaction studies indicate that C-terminal substrate binding domain (SBD) of Siah2 is involved in the binding to PHD3 irrespective of the N-terminal ring domain. The structure-based high throughput virtual screening (HTVS) method was used to identify potential small molecule inhibitors and we have identified five drug-like lead molecules specific for the Siah2 using 14400 drug-like subsets obtained from the Maybridge database, which might inhibit the interaction between Siah2 and PHD3. The lead molecules from screening were then tested in silico for their pharmacokinetic properties and percent human oral absorption using QikProp. Further, pharmacokinetic analysis based on Lipinski's rule of five which is based on ADMET (absorption, distribution, metabolism, excretion and toxicity) properties suggested potential utility of these compounds as drug leads. Docking studies were carried out to analyze the binding conformations of the identified lead molecules towards the Siah2 which reveals that Ser39 residue of SBD may be the key amino acid residue interacting with these ligands necessary for the induction of Siah2 activity. These results set the stage for the development of a workflow for selection of domain specific drug development. Five potential drug-like molecules specific to the SBD domain were eventually selected on the basis of binding characteristics, docking energy and ADMET properties. Further in-vivo and in-vitro experimental studies to investigate the inhibitory potential of these lead drug-like small molecules on this ligase and its binding are under progress. 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 A43.
Abstract 4070: Mutant tristetraprolin enhances growth factor downregulation and inhibition of cell growth in malignant glioma
Authors: Esther A. Suswam, John J. Shacka, Xiaowen Zhang, Liang Lu, Xuelin Li, Lei Zheng, Ying Si, Peter H. King
Journal: Cancer Research (2010)

Abstract Background: Tristetraprolin (TTP) negatively regulates short-lived mRNAs by binding to AU-rich elements in the 3′ untranslated region (3′UTR). A number of mRNA targets, including vascular endothelial growth factor (VEGF), and interleukin (IL)-8, play an important role in tumor progression. We have shown previously that TTP downregulates IL-8 and VEGF in malignant glioma (MG) cells via RNA destabilization. In primary glioblastoma tumors, TTP is heavily phosphorylated which may render the protein less active. Hypothesis: We postulate that the destabilizing effect of TTP on target growth factor mRNAs is held in check by hyperphosphorylation which leads to altered subcellular localization and protein stability. Methods: Wild-type TTP and two mutant forms in which select serines were exchanged with alanines were cloned with a Flag epitope into pTRE2 and pEGFP vectors. U251 Tet On MG cells were transfected with pTRE2–TTP plasmids to produce stable clones. TTP expression was induced using doxycycline. Cellular location was assessed by fluorescence microscopy and Western blotting. Protein stability was measured by assessment of TTP levels following cycloheximide treatment. VEGF and IL-8 mRNA and protein levels were measured by qRT-PCR and ELISA. For assessment of RNA half-lives, cells were treated with actinomycin D. Cell growth, proliferation and cell viability were assessed using biochemical assays, soft agar, and Trypan Blue method. Results: Both IL-8 and VEGF mRNA levels were significantly lowered in the mutant TTP clones compared to wild-type. Half-lives of these mRNAs were also shortened, and ELISA analysis showed a correspondingly greater decrease in protein expression. There was a marked impact on cellular phenotype with greater inhibition of proliferation and loss of cell viability. A Soft agar colony formation was decreased by five-fold in mutant clones versus wild-type and a greater than ten-fold decrease versus the parent cell line. With TNF-α, there was a significant shift of mutant TTP to the nuclear compartment compared to WT TTP. Treatment with cycloheximide revealed that the WT TTP was less stable compared to dephosphorylated mutant. Conclusion: Removal of key serine residues from TTP enhances its function as an RNA destabilizer of VEGF and IL-8 mRNs and as a negative regulator of tumor cell growth in MG. 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 4070.
FDG Uptake in Liposclerosing Myxofibrous Tumor Causes Upstaging of Hodgkin Lymphoma
Authors: Jongho Kim, Wengen Chen, Charles Resnik, Vasken Dilsizian, Qing Chen, Amy S Kimball
Journal: Clinical Nuclear Medicine (2014)

A 22-year-old woman with Hodgkin lymphoma underwent a staging 18F-FDG PET/CT scan, which showed an intense uptake in the right proximal femur, in addition to FDG-avid mediastinal and cervical lymph nodes. The patient thus was diagnosed with stage IV lymphoma with bone marrow involvement. Postchemotherapy restaging scan showed complete resolution of nodal uptake but persistent activity in the right femur. Radiography and biopsy confirmed liposclerosing myxofibrous tumor.
Articulated dental cast analysis of asymptomatic and symptomatic populations
Authors: Frank E Cordray
Journal: International Journal of Oral Science (2016)

Dental instrumentation has long provided insight into the mechanism of musculo-skeletal function of the gnathic system. While large population studies associate dental arch displacement (DAD), especially laterally, with symptoms, mandibular condyle displacement (CD) resulting from DAD has not been targeted as possibly etiologic in the production of common muscle contraction headache (CMCH) and temporo-mandibular dysfunction (TMD). The objective was to evaluate the three-dimensional nature of DAD and CD between the seated condylar position (SCP) and the intercuspal position (ICP) and to compare results derived from large deprogrammed asymptomatic and symptomatic populations. A total of 1 192 sets of dental casts collected from asymptomatic and symptomatic populations were articulated in the SCP. The initial occlusal contact, DAD, and condylar displacement were evaluated for frequency, direction, and magnitude of displacement between the SCP and ICP. The data revealed significant displacement between the SCP and ICP of the condyles (displaced most frequently inferior (down) and posterior (distal)) and substantially increased frequency and magnitude of displacement of the dental arches (with posterior premature occlusal contacts, increased overjet, decreased overbite, midline differences, and occlusal classification changes) in symptomatic subjects. These discrepancies were statistically significant and clinically significant. The data support the concept of increased DAD and CD with dysfunction. Transverse condylar displacement, commonly presenting with dental cross bite, may be associated with CMCH and TMD. Displacement of the mandibular condyle may be an etiologic factor in CMCH and dysfunction of the temporo-mandibular joint.
EFICACIA Y SEGURIDAD DE LA ESFINTEROTOMÍA MAS ESFINTEROPLASTIA CON BALONES DE GRAN CALIBRE EN EL TRATAMIENTO DE LA COLEDOCOLITIASIS DE DIFÍCIL EXTRACCIÓN. -
Authors: I Aured De la Serna, I Calvo Morillas, R Uribarrena Amezaga, C Lapresta Moros, M Lázaro Ríos, R Narro, K Aspuru Rubio, T Cabrera Chaves, J Sebastián Domingo, R Uribarrena Echebarría
Journal: Endoscopy (2011)

Objetivo: En casos de coledocolitiasis múltiple, de gran tamaño o cuando la papila impide realizar una esfinterotomía endoscópica suficientemente amplia, puede resultar difícil la extracción de los cálculos del colédoco. Analizaremos la seguridad y eficacia de dilatar la esfinterotomía con balones de gran calibre en el tratamiento de coledocolitiasis de difícil extracción, comparándolo con la EE.
FRI0121 The Comparative One-Year Drug Survival Rate of Tumor Necrosis Factor Inhibitors in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis; Results from TURKBIO Registry: Table 1.
Authors: I. Sari, U. Kalyoncu, A.M. Onat, O.N. Pamuk, O. Karadag, B. Kısacık, S. Şenel, F. Saritas, I. Ertenli, S. Kiraz, P. Cetin, F. Onen, N. Akkoc
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Three different anti–tumor necrosis factor α (anti-TNFα) drugs (infliximab, etanercept, and adalimumab) are approved for patients with rheumatoid arthritis (RA) and particular ankylosing spondylitis (AS) in Turkey. Their efficacy has been well shown not only in randomized controlled clinical trials, but also in clinical practice setting. Comparative drug survival analyses across different diagnoses have been published in few studies. No data is yet available for the Turkish population. <h3>Objectives</h3> The primary goal of this study was to compare the 1-year drug retention rates of TNF inhibitors in patients with AS and RA who were enrolled in the Turkish biologic registry, TURKBIO. <h3>Methods</h3> TURKBIO biological registry, which was established in October 2011, is a nationwide biological registry contributed by 10 different centers across Turkey. As of December 2013, 3380 patients who are receiving biologic treatment for RA (n=1355, 40.1%) or AS (n=2025, 59.9%) were enrolled in the database. However this analysis includes only 789 patients, who initiated biologic treatment after the participation of the individual centers in TURKBIO. Demographic and clinical data and previous or current treatment with DMARDs and biological drug durations are stored in the database. <h3>Results</h3> Of the 789 patients included in this analysis, 386 patients (48.9%) were being treated for RA and 403 patients (51.1%) for AS. There were significant differences between the two groups in regard with age, gender distribution, DMARD use at baseline and DMARD use at last visit (Table). Preference for individual anti-TNF agents were also different between the RA and AS patients; infliximab, etanercept and adalimumab were used by 11.7%, 28.2% and 25.1% of the RA patients, respectively and 26.3%, 32.8% and 32.8 of the AS patients, respectively. AS patients had a shorter diagnosis duration than the RA patients. One year drug survival for the first anti-TNF agent was 60.8% for RA, and 78.3% for AS (P=0.0007). <h3>Conclusions</h3> The proportion of AS patients treated with biologic agents in the TURKBIO registry was slightly higher than that of RA. These results also suggest that the drug survival rate of anti-TNF agents in AS patients seems to be higher than in RA. This finding may explain the higher percentage of AS patients in the whole registry population, which included patients who had started biologics before the establishment of the TURKBIO registry. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5832
Risk of self-harm and nonfatal suicide attempts, and completed suicide in patients with psoriasis: a population-based cohort study
Authors: A. Egeberg, P.R. Hansen, G.H. Gislason, L. Skov, L. Mallbris
Journal: British Journal of Dermatology (2016)

Psoriasis is a common inflammatory skin disease, and inflammation may affect suicidal behaviour. Current data on the incidence and risk of suicidal behaviour in patients with psoriasis are scarce. We investigated the association between psoriasis and the risk of self‐harm and suicide attempts and suicides. All Danish patients aged ≥ 18 years with mild or severe psoriasis (cases) from 1 January 1997 to 31 December 2011 were matched on age, sex and calendar time 1 : 5 with healthy controls. The outcome was a diagnosis of self‐harm or a nonfatal suicide attempt, or completed suicide. Incidence rates per 10 000 person‐years were calculated, and incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated by Poisson regression models. The study cohort comprised 408 663 individuals, including 57 502 and 11 009 patients with mild and severe psoriasis, respectively. In total 280 cases of self‐harm or suicide attempts, and 574 suicides occurred during follow‐up. There was no increased risk of self‐harm or suicide attempts in patients with mild psoriasis (IRR 1·01, 95% CI 0·17–2·01), but this risk was significantly increased in severe psoriasis (IRR 1·69, 95% CI 1·00–2·84). There was no increased risk of suicides in mild (IRR 1·05, 95% CI 0·84–1·32) or severe psoriasis (IRR 0·78, 95% CI 0·45–1·36). Similar results were found when suicides were confirmed by official forensic investigations, and when psoriasis was compared with atopic dermatitis. We found limited evidence to suggest an increased risk of self‐harm and nonfatal suicide attempts in patients with psoriasis. Importantly, after adjustment for psoriatic arthritis this risk was no longer significantly increased. The risk of completed suicide was also not increased, regardless of psoriasis severity.
Meckel's Diverticulum
Authors: Alfred S. Berne
Journal: New England Journal of Medicine (1959)

IN 1812 Meckel described the congenital diverticulum of the small intestine that now bears his name. Although this lesion has been discovered in 1 or 2 per cent of various autopsy series, notoriously the roentgenographic demonstration of Meckel's diverticulum is not frequently accomplished.1 2 3 4 Up to 1958 no more than 30 or 40 cases so diagnosed had been reported.5 6 7 8 9 10 11 12 13 14 Many physicians, including radiologists, have commented upon the infrequency of the roentgenologic diagnosis and have made statements such as the following: "Roentgenologic examinations have been demonstrated as practically useless in attempts to visualize the lesion [Meckel's diverticulum]...."15 16 17 18 19 20 This report will serve to . . .
PTU-155 Lessons Learnt from the First 50 Consecutive Primary Laparoscopic Nissen Fundoplications in a Single Surgeon’S Practice
Authors: L Sanyaolu, L Cleveland, A Rasheed
Journal: Gut (2013)

<h3>Introduction</h3> Laparoscopic Nissen fundoplication (LNF) is widely used in the surgical management of gastroesophageal reflux disease (GORD). However, it is a complex operation that requires advanced laparoscopic skills. Very few studies report objective testing postoperatively; those that do show high rates of failure within the first 1–3 years following surgery. Complications and failures of LNF are directly related to surgeon’s experience and the learning curve has been identified as a confounding factor. The Aim of this is analyse a single surgeon’s first 50 consecutive primary LNFs experience. The data will be used to attempt to define the learning curve (LC) for LNF using success as surrogate marker of competency, and of how this may influence future training. <h3>Methods</h3> All the patients who underwent antireflux surgery were entered into a prospectively maintained database. The procedures were performed using a five-trocar technique and with 10-/5- mm ports and instruments. Surgical outcome was recorded using the Viscik symptom evaluation tool and complications graded according to the Dindo-Clavien classification. Captured parameters included patients’ demographics, BMI, ASA grade, pre-operative investigations, operating time, indications for surgery, laparoscopic to open conversion rates, re-operation rates, morbidity, and mortality, follow up, and further investigations and interventions. Systematic case per case retrospective note analysis was performed. <h3>Results</h3> The first fifty consecutive cases underwent primary sutured cruroplasty and Nissen’s fundoplication by or under the direct supervision of the operating surgeon. One patient was abandoned due to inability to access the hiatus and one converted to open for bleeding from the omentum upon insertion of the primary port (both were during the first 25 cases). Three patients suffered with complete post-operative dysphagia, 2 resolved during the first 48 hours and one was converted to Toupet’s (they were all during the first 25 cases). On follow up, one patient was re-operated and undone two years following the procedure for continuous epigastric pain with good outcome and one who had belching as a predominant symptom did not derive any symptomatic benefit from the procedure. <h3>Conclusion</h3> Laparoscopic antireflux surgery “a reparative procedure” is not a natural extension of laparoscopic cholecystectomy “an extirpative procedure”. Different dissecting skills and mastery of intracorporeal suturing and knot tying are necessary for laparoscopic antireflux surgery. The long and steep learning curve can be modified but not eliminated by systematic training and direct supervision during the first 25 cases. Occasional surgical treatment of GORD must be discouraged in order to achieve best possible surgical outcomes. <h3>Disclosure of Interest</h3> None Declared
AB0798 Association between Knee Osteoarthritis and Achilles Tendinopathy
Authors: T. Reitblat, O. Reitblat, L. Kalichman
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In our clinical practice, we noticed that individuals with symptomatic knee osteoarthritis (OA) frequently complain on pain or swelling above Achilles tendon. We found no studies that evaluated association between knee OA and Achilles tendon pathology. <h3>Objectives</h3> To explore the association between knee OA and changes in Achilles tendon. <h3>Methods</h3> Cross-sectional observational cohort study was performed in Rheumatology Unit, Barzilai Medical Center, Ashqelon, Israel. The convenience sample of 30 knee OA (Kellgren-Lawrence (K-L) score ≥2) female patients complaining on unilateral pain was recruited. For each patient, demographic data, K-L score, sonographic evaluation of femoral cartilage thickness and Achilles tendon width, and Western Ontario and McMaster Osteoarthritis (WOMAC) Index were collected. To evaluate the association between femoral cartilage thickness, K-L score, WOMAC parameters, and Achilles tendon width we used Pearson9s correlation and linear regression analysis. <h3>Results</h3> Significant association was found between Achilles tendon width and WOMAC total score (r=0.490, p=0.006), pain (r=0.416, p=0.022), and functional (r=0.452, p=0.012) scores (but not stiffness score (r=0.242, p=0.198)) in the affected side. Associations remained significant after adjustment for age and body mass index. No associations between similar parameters were found in the unaffected side. No associations were found between K-L score, cartilage thickness and Achilles tendon thickness in affected and in unaffected sides. No associations were found between K-L score or cartilage thickness (at affected or unaffected side) and any parameters of WOMAC. <h3>Conclusions</h3> This is a first study that evaluated the association between knee OA parameters and Achilles tendon width. There are previous studies that found that weakness of quadriceps muscle is associated with knee OA. It is possible that gastrocnemius muscle whose attachments are also proximate the knee joint participates in knee stabilization. Stress forces that are implied on the muscle to stabilize osteoarthritic knee may cause structural changes in Achilles tendon. Interestingly, the Achilles tendon width was associated with pain and function of ipsilateral OA knee, but not with radiographic OA severity score (K-L) and not with cartilage thickness. Therefore, the sense of pain in the affected joint may be not only due to cartilage changes in the affected joint, but also because of simultaneous changes in Achilles tendon. Comprehensive assessment of Achilles tendon should probably be part of routine knee OA evaluation. The findings of this research provide a basis for further studies with larger sample size, and using different study designs. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1619
Abstract 2132: Analysis of adenylate cyclase 6 in HMBA induced K562 cell megakaryocyte differentiation.
Authors: Shin Hua Jiang, Chiu Yi Ho, Tai Lin Lee, Yun Shiang Chang, Wei Tung Huang, Meng Feng Tsai, Ang Yuan
Journal: Cancer Research (2013)

Abstract Leukemia is a hematopoietic stem cell disorder and leukemia patients suffer their lost in functional blood cell and the ratio of non-function cell increased. K562 cell was isolated from the pleural effusion of the leukemia patient and was used as a model cell line to study the relationship between the blood cell differentiation and signal transduction. In this report, three different inducers, huangqi (Astragalus membranaceus) extract, chemicals Hemin and HMBA were used to induce K562 cell differentiation and several cluster of differentiation (CD) marker were used to identify the cell linage. Two megakaryocyte markers were up-regulated in these treatments. The CD61, a late marker, was highly expressed in HMBA treated cell and CD41, an earlier marker, was identified in huangqi and HMBA treated cell. In former report, the Gi2α and Gsα was induced by the HMBA administration. Since both G proteins affect their downstream effector, adenylate cyclases (ADCYs), the ADCYs that could be participated in the pathway were examined by RT-PCR. The ADCY1 and ADCY6 were up-regulated in the HMBA-induced K562 cell. The ADCY6 was further studied because it coupled to calcium ion channel. The recombinant ADCY6 transfected cells were treated with three inducers, the results showed that all inducers induceed CD61 expression especially in HMBA treated sample. Also, the CD61 gene was 25 times higher expression as the parental cell. The results imply that the signals activated from HMBA and ADCY6 together may participate in the megakaryocyte differentiation. The study suggested that K562 cells can change the cell destination through the ADCY isoforms expression and other signal genes. These results may be used as the reference of the drug discover for leukemia treatment. Citation Format: Shin Hua Jiang, Chiu Yi Ho, Tai Lin Lee, Yun Shiang Chang, Wei Tung Huang, Meng Feng Tsai, Ang Yuan. Analysis of adenylate cyclase 6 in HMBA induced K562 cell megakaryocyte differentiation. [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 2132. doi:10.1158/1538-7445.AM2013-2132