tbuckley/cabot-search huggingface dataset:
PTH-107 A Preliminary Study Of The Effects Of Obeticholic Acid, A Farnesoid X Receptor Agonist, In Patients With Chronic Diarrhoea Secondary To Crohn’s Ileal Disease
Authors: JD Nolan, C Vassie, IM Johnston, D Shapiro, JR Walters
Journal: Gut (2014)

<h3>Introduction</h3> Chronic diarrhoea occurs frequently as a result of excess faecal bile acid (BA) loss. Secondary bile acid diarrhoea (SBAD) is common in Crohn’s disease with ileal inflammation and/or resection. The normal ileum produces Fibroblast Growth Factor 19 (FGF19) in response to BA absorption and farnesoid X receptor (FXR) activation. FGF19 acts as a hormonal regulator of hepatic BA synthesis. We showed previously in 10 patients with primary bile acid diarrhoea, diagnosed by 7d SeHCAT retention &lt;10%, that the semi-synthetic BA and potent FXR agonist obeticholic acid (OCA) significantly increased low FGF19 levels producing significant clinical improvement. We aimed to see if these findings could be extended to patients with SBAD due to Crohn’s and in idiopathic diarrhoea controls. <h3>Methods</h3> Out of 32 patients recruited to this pilot trial, 8 SBAD patients (6F:2M, median age 45, ileal resection 0–48 cm, median 22.5 cm, and/or SeHCAT &lt;11%), and 7 controls (2F:5M, SeHCAT 16–35%, median 25%) received OCA 25 mg daily for 2w after a 2w run-in period. BA sequestrants were discontinued. Symptoms were recorded and a stool index calculated from frequency, stool form and loperamide use. On the first and last days of OCA therapy, blood samples were assayed for FGF19, total BA levels and the BA precursor, 7αOH-4-cholesten-3-one (C4) in fasting and for 6h after OCA and meals. <h3>Results</h3> In the SBAD group, 7 out of 8 patients showed positive but variable changes in stool form and stool index (both p = 0.07, Wilcoxon). Pain frequency (p = 0.05) and severity (p = 0.07) improved. Ileal resection length was related to the change in stool number (r = 0.78, p = 0.01, Spearman), index (r = 0.63, p = 0.05) and urgency (r = 0.68, p = 0.03) so that those with the smallest resections had the greatest improvements. Increases in FGF19 fasting and post-prandial levels were relatively small except in 2 patients, but were associated with improvements in urgency (r=‑0.93, p &lt; 0.01). The reductions in post-prandial BA response (p = 0.01), fasting and peak BA values were significantly greater in those with shorter resections. C4 was related inversely to FGF19 and positively to the resection length. By contrast in the diarrhoea controls, there were no significant changes in clinical symptoms or FGF19. However BA responses were lower (p = 0.03) and significant relationships between FGF19 and BA responses were found. <h3>Conclusion</h3> This pilot study has shown that OCA produces clinical benefit in many patients with chronic diarrhoea including those with SBAD, particularly with short resections, but not in idiopathic controls. Further trials are warranted. <h3>Disclosure of Interest</h3> None Declared.
Obstructive Sleep Apnea
Authors: Patrick J. Strollo, Robert M. Rogers
Journal: New England Journal of Medicine (1996)

Our understanding of the nature and consequences of upper-airway obstruction in adults during sleep has evolved considerably over the past two decades. Sleep apnea — defined as repeated episodes of obstructive apnea and hypopnea during sleep, together with daytime sleepiness or altered cardiopulmonary function — is common.1 Epidemiologic studies estimate that the condition affects 2 to 4 percent of middle-aged adults.2 Only a small portion of the cases in this group of adults have been diagnosed; this is related to insufficient awareness of sleep apnea among physicians and the public at large.3 DefinitionsThe manifestations of upper-airway closure during sleep . . .
Mutations of the Spliceosome Complex Genes Occur In Adult Patients but Are Very Rare In Children with Myeloid Neoplasia
Authors: Shinsuke Hirabayashi, Jessica Moetter, Kenichi Yoshida, Michael Heuser, Henrik Hasle, Alexandra Fischer, Brigitte Strahm, Brigitte Schlegelberger, Irith Baumann, Felicitas Thol, Jan Stary, Franco Locatelli, Marco Zecca, Markus Schmugge, Michael Dworzak, Marry M. van den Heuvel-Eibrink, Barbara De Moerloose, Seishi Ogawa, Christian M. Flotho, Charlotte M. Niemeyer, Marcin W. Wlodarski
Journal: Blood (2011)
LEFT ATRIAL STRAIN IS A POWERFUL PREDICTOR OF ATRIAL FIBRILLATION RECURRENCE AFTER CATHETER ABLATION: STUDY OF THE HETEROGENEOUS POPULATION WITH SINUS RHYTHM OR ATRIAL FIBRILLATION
Authors: Risako Yasuda, Mitsushige Murata, Rachel Roberts, Hanako Tokuda, Keiko Suzuki, Hikaru Tsuruta, Seiji Takatsuki, Takayuki Abe, Keiichi Fukuda
Journal: Journal of the American College of Cardiology (2014)
AB0391 Title: Evolution of Optimized Patients in Biological Treatment with Adalimumab and Etanercept:
Authors: J.M. Blanco, M. Garcia Vivar, E. Ruiz Lucea, C. Gomez Arango, E. Galindez Aguirregoikoa, J. Gorordo Olaizola, I. Torre Salaberri, O. Fernandez Berrizbeitia, F. Garcia Llorente, E. Ucar Angulo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biological therapy has changed the management of patients with inflammatory disease, but with a great increase of pharmaceutical costs and emergence of potential adverse effects. At the end of 2011 we established an internal protocol in management and dose optimization of the patients with biological treatment. Those patients with inflammatory disease who achieve remission by clinical and laboratory parameters and show no ecographic activity (arthritis, enthesitis), receive a reduction of dose. Patients with etanercept 50 mg sc. weekly reduce dose to 25 mg, and patients with adalimumab at a dose of 40 mg/2 weeks increase injection interval to 3 weeks. Thus we have achieved optimization of 20% in 2012, which is close to 40% at the end of 2013. <h3>Objectives</h3> To show that there is not a significant clinical or analytical worsening in our optimized patients, considering basal data at the time of optimization and six months later. <h3>Methods</h3> Retrospective analysis of data from clinical records and our database of 105 patients treated with etanercept and adalimumab, optimized from 2011, considering lab tests results (ESR, RCP), disease activity (DAS 28, BASDAI), functional capacity indexes (HAQ, BASFI), and GP E (global patient evaluation of the disease). We used SPSS 21.0 for statistical analysis. <h3>Results</h3> 105 patients (53 female and 52 male), 31% with rheumatoid arthritis (RA), 27,5% with ankylosing spondylitis (AS), 37,7% wiyh psoriatic arthritis (PA), and 3,8% juvenile idiopatic arthritis (JIA), most of them with a longstanding disease, with a mean of 152,47 months of evolution (18-638). Table 1 shows both, the basal findings and the results from six months later. Furthermore, 32,4% of patients had a DAS 28 increase over 0,6, but in only 14,7% DAS 28 increase resulted over 1,2. BASDAI an BASFI increases &gt;2 from basal occurred in 4,4% of patients. EGP increases &gt;20 from baseline occurred in 15% of patients. <h3>Conclusions</h3> Our patients optimized with etanercept and adalimumab maintain remission criteria based on clinical and laboratory parameters at six months. So, optimization seems to be safe and cost effective in an important amount of patients with longstanding disease. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5931
Complications of Endoscopic Biliary Sphincterotomy
Authors: Martin L. Freeman, Douglas B. Nelson, Stuart Sherman, Gregory B. Haber, Mary E. Herman, Paul J. Dorsher, Joseph P. Moore, M. Brian Fennerty, Michael E. Ryan, Michael J. Shaw, Jeffrey D. Lande, Alfred M. Pheley
Journal: New England Journal of Medicine (1996)

Endoscopic sphincterotomy is commonly used to remove bile-duct stones and to treat other problems. We prospectively investigated risk factors for complications of this procedure and their outcomes.
Immunopathology of Follicular Lymphomas
Authors: Roger Warnke, Ronald Levy
Journal: New England Journal of Medicine (1978)

To investigate whether follicular lymphoma has a monoclonal origin, we stained frozen tissue sections from 22 afflicted patients for kappa and lambda light chains with an immunofluorescence technic. F(ab′)2 antibody fragments were used to avoid binding by Fc receptors. In 20 cases the lymphoma nodules comprised a monoclonal population of immunoglobulin-producing cells. The nodules were usually surrounded by a normal, polyclonal population of B lymphocytes. Reactive lymphoid follicles were easily differentiated from lymphoma nodules on the basis of clonality. Eight cases contained multiple immunoglobulin heavy chains. All the lymphoma nodules in the same tissue or in multiple tissues in the same patient showed identical light-chain and heavy-chain staining even if different histologic subtypes were identified. Follicular lymphoma is the outgrowth of a single clone of immunoglobulin-bearing cells that retain the tissue-homing characteristics of B lymphocytes. (N Engl J Med 298:481–486, 1978)
A Pain in the Brain
Authors: Amanda J. Redig, Anand Vaidya, Don C. Bienfang, Tracey Milligan
Journal: New England Journal of Medicine (2013)

A 54-year-old woman presented with a headache that had started 8 days earlier. She had awoken with stabbing, squeezing pain around her entire head. She rated the pain at 10 on a scale of 0 to 10 (known as 10/10), with 10 representing the worst pain imaginable. The pain was not alleviated by nonsteroidal antiinflammatory drugs (NSAIDs). She reported having had no headache on going to sleep . . .
Abstract 4708: Anti-tumor phenotype of tumor-associated macrophages are induced by COX-2 inhibition via the up-regulation of IFN-γ.
Authors: Yuki Nakanishi, Masato Nakatsuji, Hiroshi Seno, Tsutomu Chiba
Journal: Cancer Research (2013)

Abstract BACKGROUNDS AND AIMS Macrophages are a major constituent in tumor stroma, and macrophages infiltrating tumors are called tumor-associated macrophages (TAMs). Macrophages have a functional plasticity depending on the stimuli from microenvironment. M1 macrophages are induced by Th1 cytokines, and exerted anti-tumor function. On the contrary, M2 macrophages are induced by Th2 cytokines, and showed pro-tumor phenotype. TAMs are considered to shift from M1 to M2 during tumor progression. However, the mechanism for this M1/M2 switch is poorly understood. Cyclooxygenase-2 (COX-2)/PGE2 pathway is up-regulated in a variety of cancers including colorectal cancers, and promotes the cancer progression. COX-2 inhibition shows anti-tumor effect in familial adenomatous polyposis patients and in Apc knockout mice. Although COX-2 inhibition affects cytokine expression profiles and tumor microenvironments, the relationship between COX-2/PGE2 pathway and TAM phenotypes remains unclear. The aim of this study is to uncover the effects of COX-2 inhibition on TAM phenotypes and cytokine expression. METHODS Cytokine expression and the phenotypes of TAMs infiltrating the stroma of ApcMin/+ mouse polyps were examined by qRT-PCR and immunohistochemistry in terms of M1 and M2 dichotomy. Selective COX-2 inhibitor was administered to ApcMin/+ mice, and the effects of COX-2 inhibition on cytokine expression and TAM phenotypes were evaluated. Furthermore, by using mouse peritoneal macrophages, the direct effects of COX-2 inhibitor on Th1- or Th2-related cytokines on macrophage phenotypes were examined. RESULTS Th2 cytokines were predominant in ApcMin/+ mouse polyps, and TAMs were polarized to M2. Selective COX-2 inhibitor skewed TAM phenotypes from M2 to M1, accompanied by tumor regression in ApcMin/+ mice. Concomitantly, the expression of M1-related cytokine IFN-γ was significantly up-regulated by COX-2 inhibition, although that of M2-related cytokines IL-4, IL-13, and IL-10 was not significantly altered. Administration of COX-2 inhibitor alone was insufficient to alter the phenotypes of mouse peritoneal macrophages from M2 to M1. However, IFN-γ treatment polarized the macrophage phenotypes from M2 to M1 even in the presence of M2-related cytokines IL-4, IL-13, and IL10. CONCLUSIONS Our results suggest that COX-2 inhibition induced anti-tumor (M1) phenotype of TAMs via the up-regulation of IFN-γ, and subsequently, may suppress intestinal tumor progression in ApcMin/+ mouse polyps. Citation Format: Yuki Nakanishi, Masato Nakatsuji, Hiroshi Seno, Tsutomu Chiba. Anti-tumor phenotype of tumor-associated macrophages are induced by COX-2 inhibition via the up-regulation of IFN-γ. [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 4708. doi:10.1158/1538-7445.AM2013-4708
TCTAP C-143 Late Presentation ST-Elevation Myocardial Infarction Complicated by Post-MI Angina and Heart Failure with Unusual High Risk Coronary Anatomy
Authors: Basil Thanoon Saeed, Ali M. AlGhamdi, Ameer Al-Ajab, Ahmed Alsaileek, Waqas M. Khan, Ahmad S. Omran
Journal: Journal of the American College of Cardiology (2015)
Abstract A20: Differential rates of proliferation and apoptosis observed in human cutaneous T-cell lymphoma cell lines, in response to treatment with 9-cis UAB30, a novel rexinoid analog
Authors: Zoe M. Verney, Venkatram R. Atigadda, Craig A. Elmets, Donald D. Muccio, Clinton J. Grubbs
Journal: Cancer Research (2011)

Abstract Cutaneous T-cell lymphoma (CTCL) designates a heterogeneous group of malignancies, characterized by the infiltration and detection of transformed T-cell lymphocytes in the skin. Although there is no cure for CTCL, a wide range of treatment options have been developed for use in the clinical setting. Bexarotene, a retinoid X receptor (RXR) agonist or rexinoid, is a commonly used treatment modality for CTCL. However, documented increases in the levels of triglycerides of CTCL patients, resulting from treatment with bexarotene, point to concerns over the long-term use and efficacy of this anticancer agent. We have recently synthesized a novel rexinoid, 9-cis UAB30, which does not elevate triglycerides in vivo and have begun evaluating its use as a potential chemotherapeutic agent for the treatment of CTCL. In this study, we compared the efficacy of 9-cis UAB30 to that of bexarotene in reducing cell proliferation and inducing apoptosis, in the three human CTCL cell lines HH, MJ, and Hut78. A standard XTT assay was used to determine the rate of cell proliferation of CTCL cells. In all three lines, 9-cis UAB30 was equally and sometimes more effective than bexarotene at suppressing cell proliferation. Using an annexin V binding assay, we next analyzed the rate of apoptosis in these human CTCL lines. Interestingly, we observed the MJ cell line to be resistant to apoptosis, when treated with either compound. The HH cell line exhibited a similar increase in apoptosis, whether treated with 9-cis UAB30 or bexarotene. Finally, the Hut78 cell line showed a greater sensitivity to apoptosis, when treated with 9-cis UAB30 as compared to bexarotene. Taken together, these preliminary results indicate that 9-cis UAB30 appears to be equally if not more effective than bexarotene at suppressing cell proliferation and appears to exert differential effects on the rate of apoptosis that may be cell-line specific. These differential responses of human CTCL cells have implications for the development of next-generation, rexinoid-based therapies and reveal that 9-cis UAB30 may be a better alternative for the treatment of CTCL. 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 A20.
Abstract 4770: Delivery of doxorubicin to multi-drug resistant murine xenografts via drug-loaded micelles formed from mixtures of amphiphilic triblock copolymers
Authors: Benjamin Dulken, Tae Hee Kim, Christopher Mount, Mengyuan Du, Wayne Gombotz, Suzie Pun
Journal: Cancer Research (2012)

Abstract BACKGROUND: The toxicity of chemotherapeutic drugs is often the limiting factor in patient dosing and can be the source of severe discomfort and suffering for patients undergoing chemotherapy. For example, the anthracycline antibiotic doxorubicin (DOX) is a potent chemotherapeutic but prolonged use can also lead to permanent heart damage. Tumors can also develop resistance to DOX by increased expression of drug efflux pumps. Nanoparticle formulations of DOX have been reported to improve tumor-specific delivery via the enhanced permeability and retention (EPR) effect. METHODS: In this work, we have encapsulated DOX in polymeric micelles formed from mixtures of amphiphilic triblock copolymers. The copolymers are composed of a hydrophobic polymer segment flanked by two hydrophilic blocks. Two different copolymers were used to form the mixed micelles: a copolymer of poly(ethylene oxide) and poly(hydroxybutyrate) (PEO-PHB-PEO), and a copolymer of poly(ethylene oxide) and poly(propylene oxide) (Pluronic F127). We hypothesize that forming mixed micelles will improve drug loading and enable preparation at room temperature (where Pluronic F127 micelles are highly unstable), while facilitating drug delivery by utilizing the stability of Pluronic F127 micelles at physiological temperatures. RESULTS: We have demonstrated that the micelles formed from the mixtures of PEO-PHB-PEO and Pluronic F127 triblock copolymers provide a combination of high drug loading content and drug delivery capabilities. DOX loading for mixed micelles was greater than that for Pluronic F127-only micelles (p&amp;lt;0.05 for all mixture ratios). DOX encapsulated in mixed micelles demonstrated increased uptake in a drug resistant MDA-435-MDR cell line over free doxorubicin (p&amp;lt;.05 for all mixture ratios), while cytotoxicity of the micelle treatment was approximately equivalent to that of the free drug. Tumor treatment efficacy was assessed in mice with subcutaneous dual xenografts of MDA-435 and MDA-435-MDR (drug resistant) cell lines. Tumor suppression of drug resistant tumors was similar for encapsulated and free drug, but mice treated with micellar DOX showed no significant weight loss after treatment, while mice treated with unencapsulated DOX experienced severe weight loss after one week when compared to initial time point (18.2% +/− 2.1% weight loss, p = .0009). CONCLUSION: The cytotoxicity, drug uptake, and tumor suppression properties demonstrated by PEO-PHB-PEO/Pluronic F127 mixed micelles supports their viability as chemotherapeutic drug delivery systems for drug resistant tumors. 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 4770. doi:1538-7445.AM2012-4770
Abstract 2526: Tyrosine 656 in topoisomerase IIβ is important for the catalytic activity
Authors: Mahrukh K. Ganapathi, Adrian G. Grozav, Belinda B. Willard, Toshiyuki Kozuki, Kenichi Chikamori, Marius A. Micluta, Andrei-Jose Petrescu, Michael Kinter, Ram N. Ganapathi
Journal: Cancer Research (2011)

Abstract Topoisomerase (topo) II catalyzes topological changes in DNA. Although, both human isozymes, topo IIα and β, are phosphorylated, site-specific phosphorylation of topo IIβ is poorly characterized. Using LC-MS/MS analysis of topo IIβ, cleaved with trypsin, Arg C or cyanogen bromide (CNBr) plus trypsin we detected four +80-Da modified sites, tyrosine 656, serine 1395, threonine 1426 and serine 1545. Phosphorylation at serine 1395, threonine 1426 and serine 1545 was established based on neutral loss of H3PO4 (−98 Da) in the collision-induced dissociation (CID) spectra and on differences in 2D-phosphopeptide maps of 32P-labeled wild type (WT) and serine1395alanine or threonine1426alanine/serine1545alanine mutant topo IIβ. However, phosphorylation at tyrosine 656 could not be verified by 2D-phosphopeptide mapping of 32P-labeled WT and tyrosine656phenylalanine mutant protein or by Western blotting with phosphotyrosine-specific antibodies. Since the +80-Da modification on tyrosine 656 was observed exclusively during cleavage with CNBr and trypsin, this modification likely represented bromination, which occurred during CNBr cleavage. Re-evaluation of the CID spectra identified +78/+80-Da fragment ions (characteristic of bromination) in CID spectra of two peptides containing tyrosine 656 and tyrosine 711, confirming bromination. Interestingly, mutation of only tyrosine 656, but not serine 1395, threonine 1426 or serine 1545, decreased topo IIβ activity suggesting a functional role for tyrosine 656. Homology modeling of the region of topo IIβ (amino acids 449-1108) containing these two reactive tyrosine residues revealed that tyrosine 711 is buried, whereas tyrosine 656 is highly exposed on the surface. This region is within, or very close to the dimerization interface, which suggests that these amino acids may be critical for topo IIβ dimer formation. These results, while identifying an important tyrosine in topo IIβ, underscore the importance of careful interpretation of modifications having the same nominal mass. 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 2526. doi:10.1158/1538-7445.AM2011-2526
Benign schwannoma of the hepatoduodenal ligament
Authors: J. Pinto, M. Afonso, R. Veloso, D. Tente, S. Fernandes, L. Proença, J. Carvalho, J. Pontes, J. Fraga
Journal: Endoscopy (2011)

Schwannomas are nerve sheath tumors comprised entirely of Schwann cells, which normally produce the insulating myelin sheath that covers peripheral nerves. They are usually homogeneous tumors, frequently located in the head, neck, spinal cord, and extremities, but rarely in the retroperitoneum, representing only 6 % of all retroperitoneal tumors [1]. In a recently conducted literature review, we found only two published case reports of a schwannoma of the hepatoduodenal ligament, both in female patients over the age of 40 [2] [3] [4].
Global Allergy Forum and 3rd Davos Declaration 2015
Authors: T. Bieber, C. Akdis, R. Lauener, C. Traidl-Hoffmann, P. Schmid-Grendelmeier, G. Schäppi, J.-P. Allam, C. Apfelbacher, M. Augustin, L. Beck, T. Biedermann, C. Braun-Fahrländer, F. T. Chew, T. Clavel, R. Crameri, U. Darsow, M. Deleuran, D. Dittlein, H.-W. Duchna, L. Eichenfeld, K. Eyerich, R. Frei, C. Gelmetti, U. Gieler, S. Gilles, M. Glatz, K. Grando, J. Green, J. Gutermuth, E. Guttman-Yassky, J. Hanifin, D. Hijnen, W. Hoetzenecker, A. Irvine, A. Kalweit, N. Katoh, E. Knol, H. Koren, M. Möhrenschlager, D. Münch, N. Novak, L. O'Mahony, A. S. Paller, C. Rhyner, C. Roduit, K. Schiesser, J. Schröder, D. Simon, H.-U. Simon, M. Sokolowska, P. Spuls, J.-F. Stalder, D. Straub, Z. Szalai, A. Taieb, R. Takaoka, G. Todd, A. Todorova, C. Vestergaard, T. Werfel, A. Wollenberg, J. Ring
Journal: Allergy (2016)