tbuckley/cabot-search huggingface dataset:
THU0036 Synovial Fibroblasts Directly Induce Th17 Pathogenicity VIA the Cyclooxygenase/Prostaglandin-E2 Pathway, Independent of IL-23
Authors: S. Paulissen, J. P. van Hamburg, N. Davelaar, P. Asmawidjaja, J. M. Hazes, E. Lubberts
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Th17 cells are critically involved in autoimmune disease induction and severity. Recently, we showed that Th17 cells, but not Th1 cells, from patients with rheumatoid arthritis (RA) upon interactionwith RA-synovial-fibroblasts (RASF) directly induced autocrine IL-17A production. This autocrine IL-17A production in turn creates a pro-inflammatory loop characterized by up-regulation of the pro-inflammatory cytokines IL-6 and IL-8, and the cartilage degrading enzymes MMP-1 and MMP-3. This loop may be an important pathway in the progression of an early inflammatory arthritis, towards a chronic destructive arthritis. However, the mechanism underlying the autocrine IL-17A production in the pro-inflammatory loop upon Th17-RASF interaction is currently unknown. <h3>Objectives</h3> To investigate the mechanism responsible for the autocrine IL-17A induction upon Th17-RASF interaction. <h3>Methods</h3> CD4+CD45RO+CCR6+ (Th17) and CD4+CD45RO+CCR6- (Th1) cells were isolated by FACS sorting from healthy controls and early RA patients. These cells were co-cultured with RASF, in the presence of neutralizing antibodies directed against soluble IL-6R (anti-sIL-6R), and/or IL-1β, and/or IL-23, etanercept, and celecoxib. Gene expression profiles were generated and supernatant was collected for cytokine analyses by ELISA. <h3>Results</h3> IL-6, IL-1β and cyclooxygenase-2 (COX-2) expressions and prostaglandin-E<sub>2</sub> (PGE<sub>2</sub>) production in Th17-RASF cultures were higher than in Th1-RASF cultures. Cytokine neutralization showed that IL-1β, IL-6 and IL-23 contributed marginally to the IL-17A induction. In contrast, treatment with celecoxib, a COX-2 inhibiter, resulted in significantly lower PGE<sub>2</sub> and IL-17A production. This effect was IL-17A specific as no inhibitory effects were found on IFN-γ and TNF-α production. Combined celecoxib and TNF-α blockade more effectively suppressed the pro-inflammatory loop than did single treatment, as shown by lower IL-6, IL-8, matrix metalloproteinase-1 (MMP-1) and MMP-3 production. <h3>Conclusions</h3> These findings show a critical role for the COX-2/PGE<sub>2</sub> pathway in driving Th17-mediated synovial inflammation in an IL-23 and monocyte independent manner. Therefore, it would be important to control PGE<sub>2</sub> in chronic inflammation in RA and other Th17-mediated autoimmune disorders. <h3>Disclosure of Interest</h3> None Declared
AB0218 Plasma heparanase levels are elevated in patients with antiphospholipid syndrome and correlate with platelet activation
Authors: K.-J. Kim, S.-J. Park, J.-Y. Kim, I.-W. Baek, C.-H. Yoon, W.-U. Kim, C.-S. Cho
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Overexpression of tissue factor (TF) and activation of the coagulation system are characteristic pathophysiology of antiphospholipid syndrome (APS). Heparanase (HPSE) is an endo-b-D-glucuronidase that cleaves heparan sulfate chains on cell surfaces and in the extracellular matrix and is released primarily from activated platelets. It has been reported that non-enzymatic activity of HPSE participates in the regulation of TF gene expression in endothelial cells and its related coagulation pathway. <h3>Objectives</h3> To evaluate plasma HPSE concentration and to determine its association with platelet activation in patients with APS <h3>Methods</h3> Plasma samples were collected from 19 clinical APS patients with history of thromboembolic events and/or fetal loss, 16 patients only seropositive for antiphospholipid antibodies (aPL), and 10 normal healthy controls. Plasma levels of HPSE, soluble P- and E-selectin were measured by enzyme linked immunosorbent assay. IgG fractions were purified from the sera of 7 APS patients and healthy subjects. Induction of HPSE release from platelets by APS IgG was confirmed by western blot. <h3>Results</h3> Plasma HPSE levels were significantly elevated in APS patients compared to controls (1046.8±240.7 <i>vs</i>. 203.6±87.1 mU/ml, <i>P</i> =0.002) and its levels of clinical APS patients were much higher than those of the patients only seropositive for aPL (1326.0±413.1 <i>vs</i>. 695.7±232.2 mU/ml, <i>P</i> =0.02). Plasma HPSE levels were positively correlated with soluble P-selectin levels (r =0.826, <i>P</i> &lt;0.001) but not with soluble E-selectin levels (r =0.186, <i>P</i> =0.307). Moreover, plasma HPSE levels showed a positive correlation with concentration of anti-b<sub>2</sub> glycoprotein I antibody in clinical APS patients (r =0.524, <i>P</i> =0.031). Platelets treated with APS IgG <i>in vitro</i> produced significantly larger amount of HPSE in a dose-dependent manner compared with control IgG. <h3>Conclusions</h3> Plasma HPSE levels were elevated in patients with APS and correlate with platelet activation, suggesting a potential role of HPSE in prothrombotic state of APS. <h3>Disclosure of Interest</h3> None Declared
AB0204 Targeting of steady state DC via DEC205 and 33D1 expands regulatory T cells but does not restore tolerance in murine lupus
Authors: J.Y. Humrich, R. Undeutsch, O. Weigert, J. Reiser, L. Seriot, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Regulatory T cells (Treg) are a promising tool for the suppression of pathogenic immune responses against self-antigens, which are detrimental in autoimmune diseases such as systemic lupus erythematosus (SLE). Dendritic cells (DC) in the steady state are important for the maintenance of peripheral self-tolerance by inducing or expanding T cell subsets with regulatory properties upon tolerogenic antigen-presentation. <h3>Objectives</h3> To induce or restore antigen-specific tolerance in murine lupus by targeting steady state DC directly <i>in vivo</i> via anti-DEC205/anti-33D1 antibodies coupled to a lupus-specific autoantigen. <h3>Methods</h3> Antibodies against the DC antigen receptors DEC205 and 33D1 were coupled to SmD1(83-119), a key autoantigen in lupus, and to ovalbumin as control antigen in our facility according to published procedures (plasmids were a kind gift of M. Nussenzweig). The potential of both fusion constructs to expand Treg in vivo, induce antigen-specific tolerance and to influence the course of disease was evaluated in (NZBxNZW) F1 model with two different doses of the respective antibody-antigen fusion protein (1μg and 5μg/mouse). CD4 T cells from lymphoid organs and were analyzed by flowcytometry either ex vivo or after antigen specific restimulation in vitro. <h3>Results</h3> Single injections of both antibody-antigen conjugates (aDEC205 and a33D1) induced an increase of CD4+Foxp3+ Treg in the lymphoid organs of lupus prone mice. However, the expansion of Treg was accompanied by an increase in conventional CD4+Foxp3- T cells with a CD44hi effector/memory phenotype and an increase in antigen-specific Th1 cells. Corresponding to this, monthly injections of both antibody-antigen conjugates in a preventive setting resulted in an earlier onset of disease and resulted in an earlier appearance of lupus-specific autoantibodies. In addition, treatment with neither antibody was capable to influence already established disease. <h3>Conclusions</h3> Although promising results had been obtained in several autoimmune models in the past, targeting of steady state DC via DEC205 and 33D1 failed to be successful in the (NZBXNZW) F1 model for lupus. This may be in part explained by the abundance of proinflammatory signals present in lupus prone mice that could induce the rapid activation and maturation of steady state DC, leading to an immunogenic presentation of auto-antigens instead of a tolerogenic one. <h3>Disclosure of Interest</h3> None Declared
Ocular Phototoxicity and Psoralen Plus Ultraviolet Radiation (320–400 nm) Therapy: An Experimental and Clinical Evaluation<xref ref-type="fn" rid="FN1">1</xref><xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: S Lerman
Journal: JNCI Journal of the National Cancer Institute (1982)

The increase in fluorescent chromophores within the human ocular lens is age related, leading to an increasingly yellow core (nucleus) that presumably results from UV radiation exposure. In approximately 10% of our population this process progresses more rapidly, resulting in the formation of the brown (nuclear) cataract. Some lenticular discoloration may be beneficial, since it enables the mature lens to filter UV and short-wavelength visible radiation, thus protecting the retina from potential photodamage. Aphakic primate retinas can be irreversibly damaged by exposure to approximately 5 mW.cm-2 long-wavelength UV (greater than 325 nm) radiation. Photosensitized damage to the lens and retina with psoralen plus UV radiation (320-400 nm) (PUVA) has been demonstrated in experimental animals, and cataracts have recently been reported in patients given PUVA therapy. A new method to screen patients for lens damage is by enhanced fluorescence measurements. This method, UV slit-lamp densitography, permits detection of lenticular photodamage at a molecular level, years before visible opacities become manifest by conventional slit-lamp examination. This procedure has also demonstrated a significantly lower level of lens fluorescence (hence decreased filtering capacity) in patients with retinal degenerative diseases, suggesting UV photodamage as a factor in the progression and perhaps pathogenesis of these conditions.
Abstract 1329: Study the novel function of Semaphorin 6A in lung adenocarcinoma
Authors: Cheng-Ying Shen, Tzu-Pin Lu, Yung-Hua Li, Wu Feng-Chang, Liang-Chuan Lai, Eric Y. Chuang, Mong-Hsun Tsai
Journal: Cancer Research (2010)

Abstract In Taiwan, most of female lung cancer patients are non-smoker (&amp;gt;90%) and most of the tumor types are adenocarcinoma. The previous studies indicated that cooking oil fumes, late menopausal ages and HPV infections have been associated with the risk of lung adenocarcinoma among non-smoking female. In order to discover novel molecular targets of non-smoking female lung cancer patients in Taiwan, the paired normal and tumor tissues were collected from 60 female non-smoking lung cancer patients for microarray analysis. From the microarray results, we found that several genes in the semaphorin family, such as SEMA3B, SEMA3G, SEMA5A, SEMA6A, and SEMA6D, were significantly down-regulated in the tumor tissues. However, the specific mechanisms of the genes in lung cancer are still unclear. Among the semaphorin genes, SEMA6A was chosen for further study. The results of quantitative real-time PCR and immunohistochemistry showed significant down-regulation of SEMA6A in lung cancer tissues. Moreover, the A549 cell line was used to further investigate the function of SEMA6A. A549 cells with overexpressed SEMA6A were identified and purified the cell membrane fraction for western blotting. A wound healing assay was also performed to address the migration ability. The result was shown that the A549 cells with over expressed SEMA6A exhibited a lower capacity to fill the gap during 24 hours incubation compared with A549 cells. In summary, our data indicated that normal lung tissues express more SEMA6A protein which might inhibit the cell migration than the cancer lung tissues. 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 1329.
Middle East Cancer Research Mirrors Peace Process
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Middle East Cancer Research Mirrors Peace Process Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 9, 3 May 1995, Page 642, https://doi.org/10.1093/jnci/87.9.642 Published: 03 May 1995
Cytogenetic response to prior treatment with interferon-α is predictive for survival after allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia
Authors: O Maywald, M Pfirrmann, U Berger, L Breitscheidel, A Gratwohl, H-J Kolb, D W Beelen, A Tobler, G Metzgeroth, S U Gnad, A Hochhaus, J Hasford, R Hehlmann, A Reiter
Journal: Leukemia (2006)
Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients
Authors: Martin B. Leon, Craig R. Smith, Michael J. Mack, Raj R. Makkar, Lars G. Svensson, Susheel K. Kodali, Vinod H. Thourani, E. Murat Tuzcu, D. Craig Miller, Howard C. Herrmann, Darshan Doshi, David J. Cohen, Augusto D. Pichard, Samir Kapadia, Todd Dewey, Vasilis Babaliaros, Wilson Y. Szeto, Mathew R. Williams, Dean Kereiakes, Alan Zajarias, Kevin L. Greason, Brian K. Whisenant, Robert W. Hodson, Jeffrey W. Moses, Alfredo Trento, David L. Brown, William F. Fearon, Philippe Pibarot, Rebecca T. Hahn, Wael A. Jaber, William N. Anderson, Maria C. Alu, John G. Webb
Journal: New England Journal of Medicine (2016)

Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients.
AB0976 Associations between ultrasonographic and radiographic features of osteoarthritis and pain – a within-person knee-matched case-control study:
Authors: I.K. Haugen, A. Mathiessen, C.N. Engen, P.S. Robinson, N. Østerås, B.E. Øiestad, L. Engebretsen, H.B. Hammer, T.K. Kvien
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Associations between osteoarthritis (OA) features and pain are difficult to study due to varying pain report between persons. A study using a within-person knee-matched design showed strong associations between radiographic knee OA and pain (1). Few studies have investigated the associations between ultrasonography (US) features of knee OA and pain. <h3>Objectives</h3> To investigate whether US features and radiographic knee OA were associated with pain using a within-person knee-matched design. <h3>Methods</h3> Eligible participants were those with knee pain (mild/moderate/severe) in one knee but not in the contralateral knee during the last week. We included 40 participants (27 women, mean (SD) age 63.5 (8.8) years) from the MUST study, which is a population-based study of persons with self-reported OA. The US exam included assessment of osteophytes (grade 0-3) at medial/lateral femur/tibia, cartilage thickness (millimetres) at the apex of medial femoral condyle, impaired cartilage quality (grade 0-2), synovitis (grade 0-3) and meniscal protrusion (grade 0-2). All US features except cartilage thickness were dichotomised as absent/present prior to analyses. Radiographic knee OA was defined as Kellgren-Lawrence grade (KLG)≥2 (0-4 scale). We examined the relation of each OA feature (exposure) to knee pain (outcome) by conditional logistic regression due to the matched nature of the data. To be able to estimate the effect of the exposure, there must be variation of the exposure within the matched set. Hence, only those with OA feature in one knee and not in the contralateral knee are informative. Due to within-person matched design, the effects of confounders at person level are eliminated. <h3>Results</h3> Twenty-eight participants had self-reported knee OA. Unilateral knee pain was present in all participants of which the majority reported mild pain (n=26). Twelve persons had US-defined osteophytes in the painful knee only, whereas three persons had osteophytes in the non-painful knee only (representing informative matched sets), and the association between osteophytes and pain was statistically significant. A strong and significant association was also found between radiographic OA and pain (table). <h3>Conclusions</h3> Radiographic knee OA was strongly associated with pain in this within-person knee-matched case-control study although the sample was small. We found that US-detected OA pathology, such as cartilage assessment and synovitis, was in less degree associated with knee pain, and significant associations were found for osteophytes only. These results may perhaps question the validity and usefulness of US in explaining pain in knee OA. <h3>References</h3> Neogi T. BMJ 2009;339:2844 <h3>Disclosure of Interest</h3> None Declared
Abstract 1104: Perturbation of 60S ribosomal biogenesis results in ribosomal protein L5 and L11-dependent p53 activation
Authors: Xiao-Xin Sun, Mushui Dai
Journal: Cancer Research (2010)

Abstract Ribosomal proteins play an important role in p53 activation in response to ribosomal stress. Multiple ribosomal proteins, including L5, L11, L23, and S7, have been shown to bind and inhibit MDM2, leading to p53 activation. However, it is not known whether ribosomal protein inhibition of MDM2 is specific to certain, but not all, ribosomal proteins. Here, we show that L29 and L30, two ribosomal proteins from the large ribosome subunit, do not bind to MDM2 and do not inhibit MDM2-mediated p53 suppression, indicating that the ribosomal protein regulation of the MDM2-p53 feedback loop is specific. Interestingly, direct perturbation of the 60S ribosomal biogenesis by knocking down either L29 or L30 drastically induced the level and activity of p53, leading to p53-depedent cell cycle arrest. Furthermore, this p53 activation requires ribosomal proteins L5 and L11, as knocking down either L5 or L11 completely abolished p53 activation induced by knockdown of L29 or L30. Consistently, knockdown of L29 or L30 enhances the interaction of MDM2 with L5 and L11. These results suggest that direct perturbation of the 60S ribosomal biogenesis activates p53 via L5 and L11-mediated MDM2 suppression. 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 1104.
“Chinese weevils” (Ulomoides dermestoides) found incidentally during colonoscopy
Authors: Leonardo Martínez-Rodríguez, Ambrosio Bernal-Méndez, Francisco Valdovinos-Andraca, Jorge Martínez-Lozano, Guido Grajales-Figueroa, Félix Téllez-Ávila
Journal: Endoscopy (2015)

A 70-year-old man underwent screening colonoscopy which revealed a nonspecific colitis characterized by several areas of "patchy" erythema ([Fig. 1]), congestion, and subepithelial hemorrhage of the mucosa of the left colon. Surprisingly, many dead insects resembling small cockroaches were seen ([Fig. 2]). These insects corresponded to the species Ulomoides dermestoides, colloquially known as "Chinese weevils." They were present in larval and adult stages, and some adult insects were undigested and appeared to be "alive" ([Fig. 3]). After the procedure, the patient informed us that he had consumed these bugs as part of an alternative therapy known as "coleotherapy," which consists of the consumption of live Chinese weevils over a period of 140 days.
Effect of Testosterone and Estradiol in a Man with Aromatase Deficiency
Authors: Cesare Carani, Kenan Qin, Manuela Simoni, Marco Faustini-Fustini, Stefania Serpente, Jeff Boyd, Kenneth S. Korach, Evan R. Simpson
Journal: New England Journal of Medicine (1997)

Recent reports of disruptive mutations of the genes for the estrogen receptor or for cytochrome P-450 aromatase1–6 have shed new light on the role of estrogen. In females the lack of estrogen due to aromatase deficiency leads to pseudohermaphroditism and progressive virilization at puberty, whereas in males pubertal development is normal. In members of both sexes epiphyseal closure is delayed, resulting in a eunuchoid habitus, and osteopenia is present.6 These findings suggest a crucial role of estrogen in skeletal maturation.1–6 We describe the responses to androgen and estrogen in a man with a novel, homozygous inactivating mutation of . . .
Coronary Arteriovenous Fistula Assessed by Radionuclide Gated Blood-Pool Tomography
Authors: V Eder, P Poret, C Marchal, P Peycher, D Casset-Senon, J M Pottier, P Cosnayp
Journal: Clinical Nuclear Medicine (2000)

The authors report a case of coronary arteriovenous fistula associated with an ectatic left anterior descending artery discovered postpartum in a young woman after cardiac insufficiency. Planar gated blood-pool imaging did not reveal any abnormality. Gated blood-pool SPECT showed the aneurysm anterior to the right ventricle and a highly dilated vessel descending from the aorta anterior to the ventricular cavities. Coronary arteriography confirmed this diagnosis. Gated SPECT is thus a more accurate study than planar gated imaging even when performed with different views.
Abstract 5416: Metabolic control of the prometastatic protein CD147.
Authors: Adonia E. Papathanassiu, Hong A. Vu
Journal: Cancer Research (2013)

Abstract Apart from a recent report suggesting that hypoxia upregulates CD147, little is known about the mechanisms responsible of the tumoral overexpression of CD147, a transmembrane and secretory glycoprotein known to promote metastasis through multiple mechanisms. Here, we report that the total and surface concentration of CD147 appear to be under metabolic control. Glucose (Glc) deprivation in MDA-MB-231 and MDA-MB-435 tumor cells leads to a decrease in the levels of total CD147 and a dramatic increase in the expression of cell surface CD147. A similar mobilization of CD147 to the plasma membrane was observed with glutamine (Gln) deprivation in MDA-MB-435 cells; when the cells were deprived of both nutrients (Glc and Gln) a dramatic increase (∼6-fold) in the cell surface expression of CD147 was observed. Plasma membrane associated CD147 is known to promote metastasis through homotypic and heterotypic interactions between cancer and stromal cells. An 80% reduction in the membrane found CD147 was observed when Gln-deprived cells were treated with ERG-240, a small molecule that inhibits the cytosolic form of BCAT, the enzyme responsible for the reversible transamination of leucine (Leu). On the other hand, Leu deprivation was shown to decrease CD147 by 6-7 fold in both cancer cell lines tested here. Treatment of the cells with ERG-240 partially reversed the increase in the levels of CD147 seen after supplementation of the Leu-deprived cells with 105 mg/L Leu. CD147 is known to possess 3 N-glycosylation sites and to exist in forms with various degrees of glycosylation; the fully glycosylated protein is associated with an increased prometastatic potential. Inhibitors of N-glycosylation, such as 2-deoxyglucose (2DG), are known to possess anticancer properties. In the present study, treatment of MDA-MB-231 cells in vitro with 10 mM 2DG led to 80% reduction of the cell surface expression of highly glycosylated CD147 without the concomitant reduction in the total concentration of CD147. In contrast, treatment of athymic female nude mice, bearing orthotopically implanted MDA-MB-231 tumors, with 125 mg/Kg 2DG twice a week led to tumors that expressed markedly increased levels of the highly glycosylated CD147 variant (Control/Treated or T/C=2.3, p=0.01). The increased expression of the protein in the 2DG-treated tumors was accompanied with an increase in the levels of circulating human CD147 (T/C=1.7, p=0.01) normalized per tumor volume. Collectively, the data point towards a metabolic control of CD147 and suggest that inhibition of tumor growth due to nutrient deprivation may initiate pathways that promote metastasis. Citation Format: Adonia E. Papathanassiu, Hong A. Vu. Metabolic control of the prometastatic protein CD147. [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 5416. doi:10.1158/1538-7445.AM2013-5416