tbuckley/cabot-search huggingface dataset:
FRI0461 Do the anti-saccharomyces cerevisiae antibodies (ASCA) modify the ankylosing spondylitis phenotype?
Authors: J. Maillet, S. Ottaviani, P. Nicaise-Roland, G. Gill, E. Palazzo, L. De Chaisemartin, O. Meyer, S. Chollet-Martin, P. Dieudé
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The <i>anti-saccharomyces cerevisiae</i> antibodies (ASCA) are serum markers in inflammatory bowel disease (IBD) either Crohn's disease (CD) or ulcerative colitis (UC), which are present in almost 50% patients with CD. In spondylarthritis (SpA), there is a lack of specific markers to help the clinician for the diagnosis and management of the disease. ASCA, often the IgA form, are found in 30% patients who have SpA even without any digestives symptoms. <h3>Objectives</h3> We performed in our department a cross-sectional study evaluating the prevalence and the influence of the ASCA status on disease phenotype. <h3>Methods</h3> 223 SpA patients (all fulfilling the ESSG criteria) were included. Demographic (age, gender, disease duration), clinical (axial and/or peripheral presentation, presence of arthritis, enthesitis, spine pain, psoriasis, uveitis, IBD), biological (<i>HLAB27</i> status) data, and use of treatments (DMARDs, anti-inflammatory drugs and anti-TNFa) were collected. For each patient, ASCA determination was performed by serum indirect immunofluorescence. Demographic characteristics, clinical features and blood tests of SpA patients ASCA positive and negative were compared. <h3>Results</h3> 223 SpA patients (mean age: 46.7±14.4 years, 54.3% men, 55% HLAB27+) were included. The mean disease duration was 105.7±116.9 months. 86% of patients had axial involvement, 70.4% had peripheral involvement. 10.6% suffered of IBD. 20.6%, 22.9% and 61.2% of patients received anti-inflammatory drugs, DMARDs or anti-TNFa respectively. Among the 223 SpA patients included, positivity of ASCA was observed in 24.7% (n= 55) (IgG: 9.4%; IgA: 21.1%). The positivity of ASCA was associated with lower frequency of <i>HLAB27</i> positivity (60.4% <i>vs</i> 38.3%, <i>P =</i> 0.011) and axial involvement (91.1% <i>vs</i> 69.9%, <i>P</i> &lt; 0.0001). Moreover, ASCA positivity was more frequently observed in patients with isolated peripheral involvement (10.7% <i>vs</i> 30.9%, <i>P</i> = 0.001), arthritis (27.3% <i>vs</i> 59.3%, <i>P</i> &lt; 0.0001) and dactylitis (9.8% <i>vs</i> 26.9%, <i>P</i> = 0.004). There was no difference between ASCA+ and ASCA- SpA patients regarding the presence of uveitis, IBD, enthesitis and psoriasis. <h3>Conclusions</h3> These findings suggest that ASCA could influence the phenotype of SpA, the ASCA positive status being associated with peripheral involvement, including dactylitis, and a decrease of frequency of <i>HLA B27</i> antigen. <h3>Disclosure of Interest</h3> None Declared
Esophageal lesions in myeloproliferative neoplasms
Authors: T. Sawada, Y. Adachi, Y. Ishii, H. Yasui, Y. Arimura, T. Endo
Journal: Endoscopy (2012)

A 67-year-old man was admitted to our hospital with worsening odynophagia. He had been diagnosed as having chronic neutrophilic leukemia based on excessive neutrophilia without blasts, anemia, hyperplastic bone marrow with normal neutrophilic maturation, and hepatosplenomegaly, without bcr/abl rearrangement [1]. Finally, he was rediagnosed as having myeloproliferative neoplasm (MPN), unclassifiable, according to the 2008 World Health Organization (WHO) classification [2]. In the 2 years after the diagnosis was made he was treated with hydroxyurea, interferon-alpha, Ara-C, and then VP-16.
Abstract 5736: Household endotoxin levels and risk of non-Hodgkin lymphoma
Authors: Jun Wang, Joanne S. Colt, Peter S. Thorne, Kiros T. Berhane, Severson K. Richard, Scott Davis, James R. Cerhan, Mary H. Ward, Leslie Bernstein, Lindsay M. Morton, Hartge Patricia, Wendy Cozen
Journal: Cancer Research (2010)

Abstract Subclinical variation in immune response may be a risk factor for non-Hodgkin lymphoma (NHL). Endotoxin is a substance located in the cell wall of gram-negative bacteria that elicits a strong innate and inflammatory immune response. It is present in large amounts in animal and human fecal material, other organic material, and cigarette smoke. We hypothesized that higher endotoxin exposure might be a risk factor for NHL because of its effect on B-cell activation. Using a population based, multi-center (Detroit, Iowa, Los Angeles and Seattle) case-control study, we evaluated the association between endotoxin levels in carpet dust and NHL risk. During an in-person interview, we collected used vacuum cleaner bags from participants who had used their vacuum within the past year and had owned at least half of their carpets or rugs for 5 years or more. Dust samples were analyzed using the kinetic chromogenic Limulus amebocyte lysate assay in the Pulmonary Toxicology Facility, University of Iowa. Endotoxin measurements from 629 cases and 467 controls were log-transformed and evaluated as both continuous and categorical variables. In order to examine a possible threshold effect, endotoxin levels among controls were categorized into tertiles, with the highest tertile further split into two equal groups based on a preliminary model search. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for sex, age, race, education, study center, and last change of vacuum bag. The highest category of household endotoxin level in dust was associated with a 35% significantly decreased risk of NHL relative to the lowest category (95% confidence interval [CI] = 0.44, 0.96). The effect was stronger for the diffuse large B-cell lymphoma (DLBCL) subtype (Odds Ratio [OR]= 0.49; 95% CI= 0.26,0.91). In conclusion, contrary to our initial hypothesis, our results suggest an inverse association between high levels of household endotoxin and NHL risk. Further studies are needed to validate this finding, ideally with endotoxin measurements prior to diagnosis. Possible mechanisms of action will be discussed. 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 5736.
FRI0207 The input of measuring of infliximab and adalimumab levels and levels of antibodies to these drugs in the management of patients with autoimmune diseases treated with anti tnf monoclonal antibodies.
Authors: Y. Braun-Moscovici, S. Ben Horin, A. Dagan, K. Toledano, D. Markovits, A. Saffouri, R. Beshara, A. Rozin, M. A. Nahir, Y. Chowers, A. Balbir-Gurman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In patients (pts) with RA and other autoimmune diseases the immunogenicity during infliximab (INF) or adalimumab (ADA) therapy lead to the r loss of response. Increasing the drug dose or shortening the re-treatment intervals has economical implications. Switching to another biological agent may be suitable. High levels of anti-INF or anti ADA antibodies (Ab) is accompanied by significant reduction in serum drug concentrations. <h3>Objectives</h3> To assess the input of measuring serum INF and ADA levels and levels of anti-INF-Ab and anti-ADA-Ab in the management of pts with RA and other autoimmune diseases trated with these drugs. <h3>Methods</h3> Trough serum levels of INF and ADA and anti-INF-Ab and anti-ADA-Ab were measured by ELISA. Anti-INF-Ab were identified by anti-human lambda chain Ab in order to minimize the interference of serum INF. Treated pts were classified into responders and non-responders based on disease activity. Statistics: descriptive statistics, T test, Spearman's correlation and multiple logistic regression analysis. <h3>Results</h3> 131 serum tests for INF and 48 - for ADA were performed in 101 pts (mean age 50.2 and disease duration 9.9 years). Among responders 51 pts received INF and 16 pts – ADA. Among non-responders 34 pts had no response and 10 pts losed response ( 24 pts – INF; 20 pts - ADA). Levels (µg/ml, mean, SD) of INF and ADA in responders 4.2(2.3) and 7(5.95) were significantly higher than in non-responders1.09(0.45) and 2.9(0.45) respectively; levels of anti-INF-Ab and anti-ADA-Ab in responders 4.59(1.0) and 0.1(0) were significantly lower than in non-responders 13.13(6.1) and 8.1(1.0). Patients with RA and ankylosing spondylitis had significantly higher Ab levels than pts with psoriatic arthritis: 8.37(3.8), 9.6(0.3) and 3.5(0)µg/ml respectively. High anti-INF-Ab or anti-ADA-Ab levels predicted treatment discontinuation. In all non-responders with low INF/ADA levels and low anti-INF-Ab/anti-ADA-Ab the shortening of re-treatment intervals lead to significant improvement (Table 1). <h3>Conclusions</h3> Assessment of immunogenicity of anti-TNF monoclonal antibodies proved useful imformation for guiding the therapy in autoimmune diseases with suboptimal clinical response. Patients with low INF/ADA levels and low levels of corresponding Ab may benefit from increasing the drug dose or decreasing of re-treatment intervals. In pts with negligible serum levels of INF/ADA and high levels of corresponding Ab the therapy should be switched to a different drug. <b>Disclosure of Interest</b>: None Declared
Feasibility Study of Forward-viewing and Curved linear-arrayed echoendoscope for pancreato-biliary system; Screening and EUS-FNA
Authors: Suzuki Rei, Irisawa Atsushi, Hikichi Takuto, Takagi Tadayuki, Tunehiko Ikeda, Sato Masaki, Watanabe Ko, Nakamura Jun, Obara Katsutoshi, Ohira Hiromasa
Journal: Endoscopy (2011)

Aim: An oblique-viewing and curved linear-arrayed echoendoscope (OV-ES) is used for not only intervention but also screening of pancreatobiliary system. It has not been investigated whether forward-viewing and curved linear-arrayed echoendoscope (FV-ES) is available for screening of pancreato-biliary system and EUS-FNA for solid pancreatic mass lesions.
P1172 “REAL-LIFE”-EXPERIENCE WITH PROTEASE INHIBITOR-TRIPLE THERAPY IN HCV GENOTYPE 1 (G1) PATIENTS (N = 131): SVR 24 RESULTS
Authors: C.R. Werner, C. Franz, D.P. Egetemeyr, N.P. Malek, U.M. Lauer, C.P. Berg
Journal: Journal of Hepatology (2014)
Correlation between preoperative serum CA 125 and surgicopathologic prognostic factors in endometrial cancer
Authors: E. Espino-Strebel, J. T. Luna
Journal: Journal of Clinical Oncology (2009)

e16524 Background: Poor prognostic factors dictating the need for extended surgical staging among endometrial cancer patients can be accurately determined only after laparotomy. An adequate preoperative work-up is thus necessary to tailor surgical treatment individually. This prospective study was conducted to determine the correlation between preoperative serum CA125 and surgicopathologic prognostic factors in endometrial cancer. It also aimed to determine the CA125 cutoff value which best predicted the prognostic factors to which it was correlated. Methods: Endometrial cancer patients diagnosed from October 2006 to July 2008 who were eligible for primary surgical treatment were included. Serum CA125 determination was done by a chemiluminescent enzyme immunoassay prior to surgery. All patients underwent laparotomy, peritoneal fluid cytology, extrafascial/radical hysterectomy, bilateral salpingooophorectomy, bilateral pelvic lymph node dissection, and para-aortic lymph node sampling. Specimens were examined for tumor differentiation, lymphovascular space invasion, depth of myometrial invasion, cervical, adnexal, and vaginal involvement, pelvic and para-aortic lymph node metastases, and peritoneal fluid cytology. Pearson r correlation test was used to evaluate the correlation of serum CA125 with the prognostic factors. A receiver operating characteristic curve was used to determine the optimal cutoff value of preoperative CA125. Results: Ninety patients with endometrioid endometrial adenocarcinoma were included. Preoperative serum CA125 was significantly correlated with deep myometrial invasion (p = 0.02), adnexal metastasis (p = 0.01), pelvic (p &lt; 0.01), and para-aortic node involvement (p&lt;0.01). It was also significantly correlated with extrauterine disease (p = 0.01). A cutoff value of 55U/mL can predict extrauterine spread with 53.85% sensitivity, 84.38% specificity and 75.56% accuracy. Conclusions: Preoperative serum CA125 has a significant correlation with deep myometrial invasion, adnexal metastasis, pelvic and para-aortic lymph node involvement, and extrauterine disease at a cutoff value of 55U/mL. It is recommended that serum CA125 determination be part of the preoperative work-up of endometrial cancer patients. No significant financial relationships to disclose.
PSYCHIATRIC AIDE SELECTION THROUGH PSYCHOLOGICAL EXAMINATIONS
Authors: EMERSON M. BARRON, H. H. DONOHUE
Journal: American Journal of Psychiatry (1951)

1. The duties of the psychiatric aide have been of a very routine nature in the past, and self-expression and initiative have not been encouraged. Under such conditions, the individual of dull normal intelligence with a tenth grade education has worked out best. We expect to remedy this situation by offering to the more intelligent aide an opportunity for further training and personal advancement in our 3 year School of Psychiatric Technology. The net result should be that the efficiency of the aide should be in direct proportion to his intelligence, educational development, and personality adjustment. 2. The psychiatric aide is one of the most important figures on the care and treatment team in all psychiatric hospitals. The aide is with the patients on his ward more hours per day than any other individual in the treatment team and is thus in a position to know the patient better than most others in the hospital. The effectiveness of therapeutic procedures will be determined to a great extent by the competency of the aide, who is required to assume many duties that are becoming more and more of a professional nature. It is thus highly important that only well-integrated individuals be accepted into this profession, so as not to endanger further the health of the patients under their care, or of themselves. 3. The Minnesota Multiphasic Personality Inventory is effective in eliminating psychopaths who apply for the position of psychiatric aide, but is ineffective in predicting the efficiency of psychiatric aides in the Arkansas State Hosptal with deviate scores in other categories of personality maladjustment. In cases that warrant a more thorough personality study, projective techniques may be used. 4. A psychological screening program of applicants for positions as psychiatric aides can be carried on in most hospitals at a relatively small cost by administering psychological examinations to groups of applicants one day per week. This can be handled even in hospitals that employ part-time psychologists.
IMPACT OF DIASTOLIC DYSFUNCTION ON POST-OPERATIVE OUTCOMES AFTER CARDIAC SURGERY: A META-ANALYSIS
Authors: Jae Hyung Cho, Adrian Hernandez, Vinay Pasupuleti, Abhishek Deshpande, Vijaiganesh Nagarajan, Hector Bueno, John Ioannidis, Eric H. Boersma, Roop Kaw
Journal: Journal of the American College of Cardiology (2015)
THU0514 Evidences of A Nontolerogenic-Proinflammatory Surface and Cytokine Phenotype in Monocytes from Patients with Psoriatric Arthritis
Authors: M.S. Chimenti, A. Bergamini, E. Baffari, A. Musto, M.D. Guarino, E. Greco, R. Perricone
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Abstract</h3> Protocadherin-15 (PCDH15), an atypical member of the cadherin superfamily, is essential for vertebrate hearing and its dysfunction has been associated with deafness and progressive blindness. The PCDH15 ectodomain, made of eleven extracellular cadherin (EC1-11) repeats and a membrane adjacent domain (MAD12), assembles as a parallel homodimer that interacts with cadherin-23 (CDH23) to form the tip link, a fine filament necessary for inner-ear mechanotransduction. Here we report X-ray crystal structures of a PCDH15 + CDH23 heterotetrameric complex and ten PCDH15 fragments that were used to build complete high-resolution models of the monomeric PCDH15 ectodomain. Using molecular dynamics (MD) simulations and validated crystal contacts we propose models for complete PCDH15 parallel homodimers and the tip-link bond. Steered MD simulations of these models predict their strength and suggest conditions in which a multimodal PCDH15 ectodomain can act as a stiff or soft gating spring. These results provide a detailed view of the first molecular steps in inner-ear sensory transduction.
Drug-Induced Reversal of Early Diabetic Microangiopathy
Authors: Rafael A. Camerini-Davalos, Carlos Velasco, Marvin Glasser, J. M. B. Bloodworth
Journal: New England Journal of Medicine (1983)

We performed three oral glucose-tolerance tests and three muscle biopsies over a period of approximately three years in 41 asymptomatic patients with chemical diabetes. At base line, 13 (32 per cent) had an increased capillary basement-membrane width in muscle. Twenty-three patients received glipizide, a new oral hypoglycemic compound, and 18 received placebo. In the patients receiving placebo the mean width of the muscle capillary basement membrane increased from 135.9 +/- 9.0 nm (S.E.M.) to 169.3 +/- 9.5 nm (P = 0.01), but in those receiving glipizide the value decreased to a level no different from that in subjects without diabetes: from 152.9 +/- 2.9 to 127.5 +/- 5.1 nm (P = 0.01). These findings suggest that microangiopathy, as indicated by an increased capillary basement-membrane width in muscle, may be present in a considerable number of patients with asymptomatic diabetes and that the changes can be reversed by early drug treatment.
Abstract 2845: Prostaglandin E receptor EP4 antagonist RQ00015986 inhibits breast cancer metastasis and protects natural killer cells from PGE-mediated immune suppression
Authors: Xinrong Ma, Dawn Holt, Namita Kundu, Kazuhiko Nonomura, Yukinori Take, Amy M. Fulton
Journal: Cancer Research (2012)

Abstract The cyclooxygenase-2 (COX-2) pathway is upregulated in breast and other malignancies. The COX-2 product prostaglandin E2 (PGE2) promotes tumor growth and metastasis by acting on a family of G-protein-coupled receptors (EP1-EP4). In breast and colon malignancies, EP4 is a principle mediator of pro-tumorigenic and pro-metastatic activities. Our previous studies demonstrated that targeting EP4 with shRNA or by pharmacologic antagonists of EP4 leads to reduced metastasis in a preclinical model of metastatic breast cancer. These studies and others establish EP4 as a potential therapeutic target, however, there is a paucity of effective EP4 antagonists available for preclinical and clinical investigation. Using a novel orally available EP4 selective antagonist, RQ00015986, we have evaluated efficacy in a syngeneic murine model of metastatic breast cancer. Murine and human breast cancer cells express EP4 and receptor occupation with PGE2 (binds all EP) or with PGE1-OH (EP4 agonist) results in adenyl cyclase activation and elevated intracellular cAMP. RQ00015986, in uM/L concentrations, was able to prevent EP4-mediated adenyl cyclase activation in murine mammary tumor cell lines 66.1 and 410.4. Breast tumor cells migrate in response to either PGE2 or PGE1-OH and RQ00015986 inhibited this response. Pretreatment of 66.1 cells with RQ00015986 prior to i.v. injection into syngeneic mice resulted in 58-69% inhibition in numbers of lung tumor colonies. Natural Killer (NK) cells are critical to the control of metastatic dissemination. The ability of RQ00015986 to inhibit lung tumor colonization was completely lost in hosts depleted of mature NK cells. We have reported previously that NK cell functions in tumor-bearing mice are severely depressed through the actions of tumor-derived PGE2 acting on EP4 receptors expressed on the NK cell. The capacities of NK cells to migrate, to produce cytokines and to lyse mammary tumor target cells are each inhibited through PGE2. In the presence of RQ00015986, the capacity of cultured NK cells to migrate and to produce Interferon-α was restored to normal levels. More interestingly, treatment of tumor-bearing mice with RQ00015986 in vivo also restored NK cell functions. This report provides evidence that a novel EP4 antagonist may have therapeutic potential in cancer and may act by antagonizing EP4 prometastatic functions on the malignant cell as well as protecting NK effector cells from PGE2-mediated immune suppression. 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 2845. doi:1538-7445.AM2012-2845
Abstract 835: Epigenetic biomarkers of chemoresistance in colorectal cancer
Authors: Cátia Moutinho, Anna Martinez-Cardús, Eva Martínez-Balibrea, Albert Abad, Manel Esteller
Journal: Cancer Research (2012)

Abstract Resistance acquisition to chemotherapeutic agents is one of the main problems that come up during cancer treatment. The mechanisms of developing resistance are poorly understood, and the causes underlying the loss of sensitivity to common chemotherapy drugs are largely unknown. Promoter hypermethylation of DNA repair genes has been demonstrated to be an excellent biomarker of sensitivity to chemotherapy agents, being the epigenetic silencing of MGMT in gliomas the most remarkable example. In this study, we have focused our research on one of the most common cancer type, the colorectal cancer (CRC). Thus, we propose to assess how DNA methylation alterations can help to explain acquired resistance to oxaliplatin (OXA) in this type of tumours. To address this issue we used LoVo OXA sensitive and resistant cell lines (LoVoS_OXA vs. LoVoR_OXA). Using DNA genomic bisulfite sequencing we found that CpG islands located at some genes promoters (candidate genes) are unmethylated in LoVoS_OXA but hypermethylated in LoVoR_OXA, being these phenomena correlated with lower mRNA and protein expression in the resistant cell line. DNA promoter methylation of theses candidate genes was then checked by Methylation Specific PCR (MSP) in 25 human CRC tumour samples obtained from patients treated with FOLFOX (5-fluorouracil; leucovorin and oxaliplatin)(blind study). Remarkably, one candidate gene promoter hypermethylation was related with worse response to chemotherapy, poor overall survival and poor progression- free survival. In contrast, promoter hypermethylation of a second candidate gene was related with improved treatment response and survival rates. Being this an ongoing project, we are performing in vitro studies in order to check if changes in promoter hypermethylation can modulate cell sensitivity to OXA drug. The results obtained in this study can help to understand the biological processes leading to chemoresistance and also to the future management of cancer patients. 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 835. doi:1538-7445.AM2012-835