tbuckley/cabot-search huggingface dataset:
AB0083 Blocade of cd28 costimulatory signal reduces autoimmune uveitis in mice model
Authors: C. Iwahashi-Shima, M. Fujimoto, S. Serada, T. Naka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A number of biologic agents have been shown to be effective for the treatment of rheumatoid arthritis (RA). Despite the improvements in the treatment for RA, less progress has been made in the treatment of uveitis associated with RA and other autoimmune diseases. Notably, because immunosuppressive agents including biologics may even worsen the autoimmune comorbid uveitis, the agents to patients with uveitis should be carefully considered. Abatacept, a selective T cell costimulation modulator targeting the CD 28 costimulatory signal, is widely used for the treatment of RA, but its effect on uveitis remains to be determined. <h3>Objectives</h3> To determine the effect of the blockade of CD28 costimulatory signal in autoimmune uveitis, mice with experimental autoimmune uveitis (EAU), a preclinical model for uveitis, were treated with various dosages and administration timings of abatacept. <h3>Methods</h3> EAU was initiated in C57BL/6J mice by immunization with interphotoreceptor retinoid binding protein (IRBP) in complete Freund’s adjuvant and administration of pertussis toxin. Various dosages (i.e. 5, 50, 500 mg/kg) and timings of administration (simultaneously with the immunization, or at the timing of disease onset) of abatacept were evaluated in this model. Severity of uveitis was assessed using clinical and histological scoring system of EAU. Three weeks after immunization, the bloods were collected to measure the levels of antibody to IRBP. <h3>Results</h3> The mice treated with abatacept simultaneously with the immunization exhibited lower clinical scores for uveitis severity compared to the mice without treatment. Administration of 50 or 500 mg/kg of abatacept markedly inhibited uveitis in mice. In contrast, administration of 5mg/kg had only marginal effect. Administration of abatacept at onset (one week after the immunization) also could reduce the severity of uveitis, but was less effective than that administered simultaneously with the immunization. Serum examination revealed that abatacept simultaneously administered with the immunization potently suppressed the anti-IRBP antibody induction, but that administered at onset did not. <h3>Conclusions</h3> Blockade of the CD 28 costimulatory signal before the onset resulted in significantly reduced ocular inflammation and anti-IRBP antibody production in mice with autoimmune uveitis. These results suggest that CD28 costimulatory signal plays a critical pro-inflammatory role in the pathogenesis of autoimmune uveitis. Because abatacept administered at onset still had an inhibitory effect on autoimmune uveitis, abatacept may be a potential therapeutic option for eye involvement in RA and other autoimmune diseases. <h3>Disclosure of Interest</h3> None Declared
Serum 2,3,7,8-Tetrachloro-dibenzo-p-dioxin Levels of New Zealand Pesticide Applicators and Their Implication for Cancer Hypotheses
Authors: A. H. Smith, D. G. Patterson, M. L. Warner, R. Mackenzie, L. L. Needham
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : The phenoxyherbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) has been widely used by professional pesticide applicators in New Zealand since before 1950. Epidemiologic studies of the risk of cancer and birth defects have been conducted in this group of workers, but little is known about the extent of their exposure to the 2,4,5-T contaminant 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), a potent carcinogen in animals., purpose: The objective of this study was to determine whether the blood serum levels of TCDD in a group of professional 2,4,5-T applicators in New Zealand were greater than those of a matched control group not involved in 2,4,5-T spraying. Methods: Of 548 men employed as professional pesticide applicators in New Zealand from 1979 through 1982, nine were selected who had sprayed pesticides, although not necessarily 2,4,5-T, for at least 180 months. These applicators had sprayed 2,4,5-T for a range of 83–372 months. We measured the blood serum levels of polychorinated dibenzo-p-dioxins and dibenzofurans, which were substituted with chlorine at the 2,3,7,8 position, in the nine pesticide applicators and in a matched group of nine control subjects. Results: The average serum level of TCDD for applicators was almost 10 times that for the matched control subjects, while the average levels of all other congeners and isomers measured in the two groups did not differ substantially. TCDD levels in eight of the nine applicators were higher than those in the control subjects (mean difference, 47.7 parts per trillion). The variation in TCDD levels among the applicators was related to their duration of work exposurs to 2,4,5-T. Conclusions: On the basis of our findings in these subjects in New Zealand, we conclude that increased risks of cancer from brief exposure to phenoxyher-bicides reported in other countries are probably not attributable to the TCDD that contaminates 2,4,5-T. We cannot determine from these results, however, whether TCDD exposure from prolonged use of 2,4,5-T poses significant health risks. [J Natl Cancer Inst 84: 104–108, 1992]
Abstract 2265: Expression of hyaluronan in human cancer tissue: A predictive biomarker for PEGPH20-mediated therapy
Authors: Ping Jiang, Salam Kadhim, Xaioming Li, Curtis Thompson, Craig McMannus, Ryan Osgood, Jennifer Anderson, Rebecca Symons, Gail Fieser, Jesse Bahn, Raija Tammi, Michael Shepard, Gregory Frost
Journal: Cancer Research (2010)

Abstract Background: Hyaluronan (HA), a ubiquitous, high-molecular-mass polysaccharide in the precellular and extracellular matrix, is frequently elevated in malignancy, and associated with aggressive disease. Interaction of HA and tumor cells may activate receptor tyrosine kinases, enhance drug resistance, and facilitate tumor progression. A pegylated recombinant human PH20 hyaluronidase (PEGPH20) has been developed to systemically target tumors that accumulated with HA. Systemic PEGPH20 administration in mice bearing PC3 tumors induced a decrease in tumor interstitial fluid pressure (IFP), a decrease in tumor water content, and an increase in tumor vascular volume by enzymatically depleting the HA from the extracellular tumor microenvironment and resulted in significant tumor growth inhibition. PEGPH20 therefore represents an innovative potential treatment approach that may provide improved therapeutic outcomes for cancer patients. Methods: The present study investigated the expression of HA in paraffin embedded human tissue from 9 tumor types as well as corresponding normal tissue by immunohistochemical staining of BioMax tissue arrays with biotinylated HA binding protein (HABP) as a probe. Staining intensity was quantified using Aperio Spectrum plus software. The correlation between HA expression and PEGPH20 response has also been explored using established preclinical models. Results: Strong HA expression was found in 87% of pancreatic, 64% of breast, 50% of multiple myeloma, 46% of NSCLC, 39% of gastric, and 22% of prostate cancer tissues, when compared with corresponding normal tissue (p&amp;lt;0.05). BxPc3 (HA high), MIA PaCa-2 (HA low) and AsPC-1 (HAlow) pancreatic tumor xenografts were evaluated for tumor growth inhibition (TGI) after systemic PEGPH20 treatment and TGI's of 25%, 9% and 15% were observed respectively. In addition, 3 prostate cancers, PC3 (HA high), MatLylu (HA high) and Du145 (HA low) were also evaluated in xenografts with significant growth inhibition shown for PC3 (72%) and MatLylu (34%). Systemic PEGPH20 treatment also induced tumor growth inhibition (60%) for 4T1 (HA high) breast cancer. Conclusion: Accumulation of HA compared to normal tissue was commonly observed and most frequent in pancreatic adenocarcinomas (87%). Furthermore, accumulation of HA was shown to predict response to PEGPH20 therapy in xenograft models (R2=0.805, p&amp;lt;0.01). This work provides strong rationale for exploring efficacy of PEGPH20 in clinical trials. 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 2265.
Abstract 486: A cancer stem cell population from a head and neck cancer show epithelial to mesenchymal transition properties and resistance to treatment
Authors: Karin B. Roberg, Linnea La Fleur
Journal: Cancer Research (2011)

Abstract Mortality in head and neck squamous cell carcinoma (HNSCC) is high due to the emergence of therapy resistance which led to local and regional recurrences that may originate from resistant cancer stem cells (CSCs). The aim of the present study was to identify cells with CSC characteristics in a HNSCC cell line and evaluate differences in CSC proteins, invasion, migration and in treatment sensitivity to radiation, cisplatin and cetuximab (a antibody blocking epithelial growth factor receptor, EGFR) between subpopulations of cancer cells. A HNSCC cell line established from a larynx cancer at the division of otorhinolaryngology at Linköping University Hospital was used in passages 8-15. Cells were cultured in Keratinocyte Media supplemented with 1% fetal calf serum. Subpopulations of cells were detected after direct immunofluorescense staning of surface CD44 and EGFR. Three different populations (CD44high/EGFRlow, CD44high/EGFRhigh and CD44low/EGFRhigh) were sorted for further investigations using a BD FACSAriaTM II Cytometer. Culturing of sorted cells demonstrated diverse morphology between the populations, where CD44high/EGFRlow cells displayed a spindle shaped morphology compared to CD44low/EGFRhigh. The subpopulations sensitivity to radiation (4Gy), cisplatin (2μg/ml, 1h) or cetuximab (30nM) was analysed 10 days after sorting by a crystal violet assay. Here, CD44high/EGFRlow cells showed the lowest sensitivity to both radiation and cisplatin. A real time PCR array was performed in order to screen for differences in gene expression between the subpopulations. Comparison of the cells with a high contra low CD44 surface expression, showed a change in mRNA levels in 19 genes, 14 up regulated and 5 down regulated. Of these 19 differently expressed genes 13 can be associated to an epithelial to mesenchymal transition (EMT) phenotype (VIM, MMP2, TIMP1, TWIST1, COL3A1, CDH1, CDH2, ITGA5, FN1, FOXC2, WNT5A, WNT5B and SPARC). Two stem cell marker genes (NANOG and SOX1) were slightly up regulated in the CD44high/EGFRlow population compared to CD44low/EGFRhigh. These populations ability for migration and invasion should now be investigated as well as differences in proliferation and clonogenic efficiency. We here identify, in a recently established HNSCC cell line, subpopulations of cells using markers suggested to characterize CSCs. More importantly, the CSC-like subpopulation displayed a lower sensitivity to radiation and cisplatin compared to the control population. 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 486. doi:10.1158/1538-7445.AM2011-486
Condition-dependent adaptive phenotypic plasticity and interspecific gene-culture coevolution
Authors: Marion Blute
Journal: Behavioral and Brain Sciences (2012)

Abstract Evolutionary socioecological theory and research proposing linking parasites with human social organization is uncommon and therefore welcome. However, more generally, condition-dependent adaptive phenotypic plasticity requires environmental uncertainty on a small scale, accompanied by reliable cues. In addition, genes in parasites may select among biologically adaptive cultural alternatives directly without necessarily going through human genetic predispositions, resulting in inter-specific gene-culture coevolution.
SAFETY OF PERFLUTREN-BASED ECHOCARDIOGRAPHIC CONTRAST AGENT ADMINISTRATION IN THE PRESENCE OF A PATENT FORAMEN OVALE (PFO): A MULTICENTER STUDY
Authors: Valentin Suma, Farhan Bajwa, Suraj Sookhu, Jyothy J. Puthumana, Issam A. Mikati, Arif Jivan, Ajay Yadlapati, Lakshmi Muthukumar, Rena Toole, Edgar Argulian, Richa Nahar, Jasjit Bhinder, Aasha Gopal, Farooq A. Chaudhry
Journal: Journal of the American College of Cardiology (2016)
Diagnostic des kystes pancréatiques par microscopie confocale: Validation externe des critères de référence
Authors: B Napoleon, AI Lemaistre, B Pujol, F Caillol, F Fumex, C Lefort, V Lépilliez, L Palazzo, M Giovannini
Journal: Endoscopy (2015)

L'endomicroscopie confocale par minisonde au travers d'une aiguille (nCLE: needle-based Confocal Laser Endomicroscopy) est une technique d'imagerie permettant de réaliser un examen microscopique in vivo et en temps réel, au cours d'une procédure d' échoendoscopie avec ponction (EE-P).
De novo arteriovenous malformation in a 4 year-old boy with headache
Authors: M. Hollingworth
Journal: International Journal of Surgery (2015)

s / International Journal of Surgery 23 (2015) S15eS134 S77 Conclusion: Patient safety in theatre is of the upmost importance, especially in high risk procedures such as those found in neurosurgery. Simple interventions can be relatively inexpensive, quick to implement and can make a significant difference to patient safety. 0071: DE NOVO ARTERIOVENOUS MALFORMATION IN A 4 YEAR-OLD BOY WITH HEADACHE M. Hollingworth. Great Western Hospital, UK Aim: Arteriovenous malformations (AVM) have traditionally been thought of as congenital lesions but this model of pathogenesis does not account for those patients in which the AVM appears to have arisen de novo. Methods: We describe the case of a 4 year-old boy who presented with headache; subsequent imaging demonstrated a Spetzler-Martin grade 3 AVM within the left superior temporal gyrus. However, this patient had previously undergone magnetic resonance brain imaging for investigation of seizures during the neonatal period, which demonstrated normal structural appearance. Conclusion: We present a case of de novo AVM in a child without preexisting cerebrovascular disease and discuss it in the context of recent advances in the understanding of AVMs. 0233: MANAGEMENT OF HEAD INJURIES PRESENTING TO A DISTRICT GENERAL HOSPITAL: COMPLIANCE WITH THE 2014 NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE (NICE) GUIDELINES L. Bond, A. Amer, R. Brown. Daisy Hill Hospital, UK Aim: A significant proportion of patients admitted with head injury suffer long term psychological and/or physical deficits. We aim to investigate our practice in managing head injuries at a district general hospital in accordance with the 2014 NICE guidelines. Methods: We prospectively investigated patients that were admitted to hospital with head injuries over a 6-week period in 2014. We collected demographics and data relating to the timescale between presentation and assessment/imaging. Results: Twenty patients were admitted over the study period. Of these, 50% were male. The most prevalent age group was above 80 years making up 50% of the total head injury admissions. Only 30% of these cases were clinically assessed within 15 minutes of presentation to A&E. In addition, only 45% of cases underwent CT imaging of the head within the recommended time. Cervical spine imaging was performed in all patients in whom this was required. However, this was performed within the recommended timeframe in only 15% of cases. Conclusion: Compliance with NICE guidance for head injuries within our hospital was suboptimal. Lack of knowledge about the recent guidelines may have contributed to these findings. Raising staff awareness in this regard will likely improve our management of head injuries. 0393: PRIMARY RESECTION OF MALIGNANT INTRACRANIAL NEOPLASMS CONVEYS A FUNCTIONAL BENEFIT IN A SELECT PATIENT COHORT J. Glasbey, C. Hayhurst. Department of Neurosurgery, University Hospital of
Scintigraphic Evaluation of Obstructing Primary Megaureter With Tc-99m MAG3
Authors: BELKIS ERBAS, STUART A. ROYAL, DAVID JOSEPH
Journal: Clinical Nuclear Medicine (1997)

Two children with the antenatal diagnosis of hydronephrosis secondary to a primary obstructed megaureter are presented. Both children were treated nonoperatively. They were observed with serial diuretic scintigrams using Tc-99m MAG3 and renal sonography. Throughout, the children have been asymptomatic. During a 3-year follow-up period, the diuretic renogram documented resolution of obstruction in one child and stable renal function with improved drainage in the other.
Abstract 4248: NANOG depletion decreases cell proliferation rate in colorectal carcinoma cells and tumor growth in nude mice
Authors: Luis A. Espinoza, John M. Jessup
Journal: Cancer Research (2010)

Abstract Nanog is a critical transcription factor involved in maintaining embryonic stem cells in a pluripotent, dedifferentiated state and expression of NANOG or its nearly identical retrogene NANOGP8 is increased in human gastric, hepatocellular, and colon cancer. Our postulate is that NANOG/NANOGP8 is critical for the functions of putative CSC in colorectal carcinoma (CRC): self-renewal, pluripotency, spherogenicity, tumorigenicity and resistance to chemotherapy. Five human CRC lines are being used in this study (HCC 2998, KM-12c, Clone A, MIP-101, CX-1). CX-1 cells are more aggressive than the other CRC because they form more spheroids from single cells and are highly metastatic after intrasplenic compared to the other CRC that are tumorigenic but weakly metastatic. qRT-PCR analysis of spheroids of CX-1 and Clone A cultured in suspension in serum free medium indicated that NANOG transcript levels were increased by 43- and 12-fold, respectively, relative to monolayer cultures while the relative increase in transcript levels of several cancer stem cell markers such as EPCAM, ALDH1A1, ALDH3A1, CD44, CD133, and CD166 was less than 5-fold except for POU5F1 and SOX2 in Clone A, which were 5- and10-fold respectively. NANOG promoter activity was low in monolayer culture in CRC stable transfectants with a GFP NANOG promoter, but consistently increased as CRC detached and formed spheroids in serum free media. Stable transfection with lentiviral NANOG shRNA decreased NANOG transcript levels and spherogenicity of Clone A and CX1 cells compared to vector controls in a single cell spherogenicity assay in serum-free medium. NANOG downregulation also induced a S phase cell cycle arrest with inhibition of ATM and WEE1 expression with associated reduction in phosphorylation of other key cell-cycle checkpoint proteins. Finally, marked tumor growth retardation was observed in NOD/SCID mice injected subcutaneously with NANOG shRNA transfected cells compared to parental or vector controls. NANOG shRNA transfected cells were also more resistant to treatment with Topotecan, a camptothecin. In summary, our data suggest that expression of NANOG/NANOGP8 occurs in human CRC and may be critical for such functions of putative CSC as spherogenicity, cell proliferation, tumor formation and resistance to chemotherapy 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 4248.
AB1152 Hemophilic arthropathy and real-life at school: Children perceptions
Authors: I. Bouaddi, D. El Badri, M. Rkain, H. Rkain, F. Allali, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To describe in children with haemophilic arthropathy, their perceptions about their scholarship situation. <h3>Methods</h3> Twenty five children (all boys, age of 11.6±3.7 years, mean disease duration of 10.8±3.4years, haemophilia severe (28%) and moderate (72%)) suffering from Haemophilia with hemophilic arthropathy (affecting at least one joint) were consecutively recruited in this study. Children were asked about their scholarship and their perceptions about their entourage at school. <h3>Results</h3> All patients were at school. Scholarship was interrupted in one child because of the hemophilic arthropathy. 92% of parents have informed the class teacher about their child disease. Schoolmates were aware of risk of bleeding in hemophilic patients in 76% of cases. Children expressed many difficulties in their daily living at school. Relation with their schoolmates was negatively affected: verbal violence and discrimination reaction from colleagues and integration difficulties at classroom in respectively 52%, 12% and 32% of cases. Difficulties at walking to school, because of the lower limb arthropathy, were reported by 48% of patients. Three patients were also very embarrassed by difficulties at writing, due the involvement of wrist and or elbow. Absenteeism was reported in all patients and was exceeding one month per year in 56% of cases. Absenteeism was mostly caused by bleeding into joints. Only 3 children have received courses during their hospitalizations. <h3>Conclusions</h3> This study suggests a high negative impact of hemophilic arthropathy on children scholarship. Even if with such chronic disabling diseases, children must be benefit of their legitimate right of scholarship. This negliged aspect of haemophilia consequences should be more clarified in our country by a larger study. This can be a first step to make a national program to assist hemophilic children throughout their scholarship. <h3>Disclosure of Interest</h3> None Declared
Criteria for decision making after endoscopic resection of well-differentiated rectal carcinoids with regard to potential lymphatic spread
Authors: C. Park, J. Cheon, J. Kim, J. Shin, B. Jang, S. Shin, Y. Jeen, S. Lee, J. Ji, D. Han, S. Jung, D. Park, I. Baek, S. Kim, D. Chang
Journal: Endoscopy (2011)

Background and study aim: Rectal carcinoids are low-grade malignancies that are usually treated by endoscopic resection. However, on pathologic examination, resection margins that are positive for carcinoid cells are frequently found. Patient outcomes were reviewed after endoscopic resection of rectal carcinoids and the clinical significance of possible residual disease, as defined by pathologic and endoscopic examination, was evaluated.