tbuckley/cabot-search huggingface dataset:
AB0999 Transthoracic Ultrasonography (TUS) in the Diagnosis of Pulmonary Fibrosis in Patients Diagnosed with Systemic Connective Tissue Disease
Authors: N. Buda, Z. Smoleńska, W. Kosiak, Z. Zdrojewski
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The aim of this study was to define the accuracy of transthoracic ultrasonography (TUS) in the diagnosis of pulmonary fibrosis. <h3>Objectives</h3> The value of TUS in pulmonary fibrosis in a patients with connective tissue disease is not as yet established. The prospective study was conducted to analyzed ultrasound changes in patients with recognized pulmonary fibrosis by transthoracic lung sonography and compare it with high resolution computed tomography (HRCT). The aim of the study was to in determine the characteristics of ultrasound in patients with lung fibrosis. <h3>Methods</h3> TUS was performed in 30 patients, average age 50 (SD 24), with diagnosed connective tissue disease and pulmonary fibrosis. The study group consisted of: systemic scleroderma (19), systemic vasculitides (3), mixed connective tissue disease (2), dermatomiositis (2), rheumatoid arthritis (1), ankylosing spondylitis (1), systemic lupus erythematosus (1), Sjogren9s disease (1). Pulmonary fibrosis was confirmed by HRCT. The study group was compared with control group (50 subjects) with normal X-ray and no history in the direction of lung diseases. <h3>Results</h3> In TUS has been reported: irregular pleural line - in 100% (0% in the control group, p&lt;0.001), fragmented pleural line - in 77% (0% in the control group, p&lt;0.001), blurred pleural line - in 52% (0% in the control group, p&lt;0.001), thickened pleural line – in 23% (0% in the control group, p&lt;0.001), artifacts of B lines less than three in one intercostal space - in 23% (0% in the control group, p&lt;0.05) and more than four B lines in one intercostal space - in 69% (0% in the control group, p&lt;0.001), and previously unrecognized artifact called the Am line- in 38% (0% in the control group, p&lt;0.001). <h3>Conclusions</h3> This study indicates the possibility of the diagnosis of pulmonary fibrosis using transthoracic sonography. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3818
The ‘GGCC’ haplotype of JAK2 confers susceptibility to JAK2 exon 12 mutation-positive polycythemia vera
Authors: D Olcaydu, R C Skoda, R Looser, S Li, M Cazzola, D Pietra, F Passamonti, E Lippert, S Carillo, F Girodon, A Vannucchi, N S Reading, J T Prchal, C Ay, I Pabinger, H Gisslinger, R Kralovics
Journal: Leukemia (2009)
1098 HCV RNA &lt;15IU/ML AT WEEK 4 IS HIGHLY PREDICTIVE OF SVR AMONG HCV G2/3 PATIENTS RECEIVING PEGINTERFERON ALFA-2A/RBV: FINAL RESULTS FROM POTENTE STUDY
Authors: H. Cheinquer, C.G.d.F. Mendes, M.P.J.S. Lima, M.L. Ferraz, E.R. Parise, F. Ruiz, F.L. Gonzales, T. Reuter, M.C. Mendes-Corrêa, A. Ferreira, F.S.B. de Araújo, M.A. Costa, A.D.L.C. Martinelli, E.G. Marins
Journal: Journal of Hepatology (2012)
Case 24-2015
Authors: Linden T. Hu, Athe M. Tsibris, John A. Branda
Journal: New England Journal of Medicine (2015)

A 28-year-old pregnant woman was admitted to the hospital in the summer because of fever, headache, neck stiffness, and fatigue. She had a faint rash on her leg, thrombocytopenia, and elevated aminotransferase levels. A diagnostic test result was received.
Endoscopic Retreatment Compared with Surgery in Patients with Recurrent Bleeding after Initial Endoscopic Control of Bleeding Ulcers
Authors: James Y.W. Lau, Joseph J.Y. Sung, Yuk-hoi Lam, Angus C.W. Chan, Enders K.W. Ng, Danny W.H. Lee, Francis K.L. Chan, Roamy C.Y. Suen, S.C. Sydney Chung
Journal: New England Journal of Medicine (1999)

After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment.
Polybrominated Diphenyl Ether Exposure and Thyroid Function Tests in North American Adults
Authors: Colleen M. Makey, Michael D. McClean, Lewis E. Braverman, Elizabeth N. Pearce, Xue-Mei He, Andreas Sjödin, Janice M. Weinberg, Thomas F. Webster
Journal: Environmental Health Perspectives (2015)

Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that are added to many consumer products. Multiple animal studies have shown PBDEs to be thyroid hormone (TH) disruptors. Epidemiologic evidence of PBDE exposure associated with TH disruption has been inconclusive.We used repeated measures to estimate associations between serum PBDE concentrations and THs in a North American adult cohort.From 2010 to 2011, we collected ≤ 3 serum samples at approximately 6-month intervals from 52 healthy adult office workers from Boston, Massachusetts, for analysis of PBDE congeners and THs.The geometric mean sum concentrations of the most prevalent PBDE congeners (BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) were 22 ng/g lipid in winter 2010, 23 ng/g lipid in summer 2010, and 19 ng/g lipid in winter 2011. BDE-47 was the predominant congener. Based on a multivariable mixed regression model, we estimated that on average, a 1-ng/g serum increase in BDE-47 was associated with a 2.6-μg/dL decrease in total thyroxine (T4) (95% CI: -4.7, -0.35). Total T4 was inversely associated with each PBDE congener. Serum concentrations of PBDEs were not strongly associated with total triiodothyronine (T3), free T4, or thyroid-stimulating hormone (TSH).These results are consistent with those from animal studies showing that exposure to PBDEs is associated with a decrease in serum T4. Because the other TH concentrations did not appear to be associated with BDE exposures, our findings do not indicate effects on the pituitary-thyroid axis. Taken together, our findings suggest that PBDE exposure might decrease the binding of T4 to serum T4 binding proteins.Makey CM, McClean MD, Braverman LE, Pearce EN, He XM, Sjödin A, Weinberg JM, Webster TF. 2016. Polybrominated diphenyl ether exposure and thyroid function tests in North American adults. Environ Health Perspect 124:420-425; http://dx.doi.org/10.1289/ehp.1509755.
A7.21 Suppression of HDAC5 Expression by Inflammatory Cytokines is Required to Promote CXCL Chemokine Production in RA FLS
Authors: C Angiolilli, AM Grabiec, LGM van Baarsen, PP Tak, DL Baeten, KA Reedquist
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Histone deacetylases (HDACs) are important regulators of gene expression and protein function in the immune system. HDAC inhibitors (HDACi) display anti-inflammatory properties in animal and in vitro models of rheumatoid arthritis (RA), as well as initial safety and efficacy in the treatment of systemic onset juvenile idiopathic arthritis. However, as most of the currently available HDACi display little selectivity or specificity for class I (HDAC 1–3, 8) and class II (HDAC 4–6, 9, 10) HDACs, the role of specific HDACs in RA is unclear. Here we examined the relationship between HDACs and inflammation in RA synovial tissue and fibroblast-like synoviocytes (FLS). <h3>Materials and Methods</h3> RNA was isolated from arthroscopic synovial biopsies from 19 RA patients. MMP-1, TNFα, IL-6, and HDAC 1–10 expression was measured by quantitative PCR (qPCR). RA FLS were stimulated with IL-1β, TNFα and LP, S and HDAC expression was measured by qPCR RA FLS were transduced with adenovirus encoding control GFP or GFP-HDAC5 or transfected with control siRNA or siRNA targeting HDAC5. Effects of HDAC5 modulation on RA FLS gene expression were analysed by custom qPCR array. <h3>Results</h3> Positive correlations were observed between RA synovial tissue expression of TNFα and HDAC1 (R = 0.651, P = 0.003) HDAC2 (R = 0.523, P = 0.022) and HDAC3 (R = 0.570, P = 0.011) and between MMP-1 and HDAC1 (R = 0.501, P = 0.029) and HDAC2 (R = 0.512, P = 0.025). A significant negative correlation was observed between synovial tissue expression of IL-6 and HDAC5 (R = –0.477, P = 0.039) and between clinical parameters of disease activity and HDAC5 (CRP: R = –0.664, P = 0.007; ESR: R = –0.556, P = 0.013: DAS28: R = –0.567, P = 0.011). HDAC5 mRNA expression was significantly and selectively reduced after RA FLS stimulation with TNFα and IL-1β, but not LPS. Of 84 genes regulated in RA FLS by IL-1β or TNFα, mRNA expression of CXCL9, CXCL10, and CXCL11 was selectively upregulated following silencing of HDAC5 expression. Conversely, mRNA expression of these chemokines was suppressed by overexpression of HDAC5 in RA FLS. <h3>Conclusions</h3> RA synovial expression of HDAC 1 and 2, but not class II HDACs, positively correlates with local inflammatory mediators, while HDAC5 expression negatively correlates with IL-6 mRNA expression and with disease activity. HDAC5 mRNA is decreased after inflammatory stimulation, and silencing of HDAC5 leads to an increase of CXCL chemokine expression in RA. FLS, an effect reversed by HDAC5 overexpression. Our results suggest a protective role for HDAC5 in RA, and that HDACi which fail to target HDAC5 may be more promising for therapeutic applications.
FRI0266 Hemodynamic complications in systemic sclerosis patients with various stages of pulmonary arterial hypertension
Authors: T. Inaba, M. Hatano, A. Yao, H. Maki, T. Imamura, T. Shiga, K. Kinugawa, R. Nagai, Y. Asano, H. Sumida, T. Takahashi, T. Toyama, Y. Ichimura, T. Taniguchi, S. Sato
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Prognosis of pulmonary arterial hypertension (PH) in systemic sclerosis (SSc) patients is poor. PH is a pathophysiological state defined by an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg as assessed by right heart catheterization (RHC) and borderline-PH is defined by mPAP ≥21 mmHg. A rise in mPAP is a late marker of the pulmonary arteries remodeling processes, and the pre-clinical phase of SSc (mPAP &lt;21 mmHg) is largely unknown. <h3>Objectives</h3> To examine the hemodynamic characteristics in SSc with various stages from normal pulmonary pressure to PH stages. <h3>Methods</h3> Eighty-eight consecutive patients with SSc (80 women and 8 men, 72 limited cutaneous SSc and 16 diffuse cutaneous SSc; mean age 62±11 yr) were assessed by RHC in a single center from May 2005 to December 2011. They were classified into four groups by mPAP (Table): (1) normal pressure (NP) group; mPAP &lt;15mmHg, (2) pre-PH group; 15≤ mPAP &lt;20mmHg, (3) borderline-PH group; 21≤ mPAP &lt;25 mmHg, (4) PH group; mPAP ≥25mmHg. <h3>Results</h3> Age was not different among 4 groups. The differences in the plasama levels of brain natriuretic peptide (BNP), peak VO2, and % vital capacity/% diffusing capacity for carbon monoxide (%VC/%DLCO) changed in parallel with PH stage. In only PH group, heart rate (HR) was significantly increased. Even in NP group, pulmonary vascular resistance (PVR) was already increased, which might imply that pulmonary arteries in SSc were impaired in the very early stage. In pre-PH group, while PVR slightly increased, cardiac index (CI) markedly decreased below normal limit. Decreases in stroke volume index (StVI) became significant in not only PH but also borderline-PH and pre-PH groups. <h3>Conclusions</h3> According to our results, pulmonary arterial remodeling progresses faster than expected from mPAP in SSc patients, and earlier pharmacological intervention may be beneficial. <h3>Disclosure of Interest</h3> None Declared
Abstract 3184: TGF-β1 signaling inhibits proliferation but promotes motility with progression to castrate-resistant prostate cancer
Authors: Fayth L. Miles, Robert A. Sikes
Journal: Cancer Research (2010)

Abstract Transforming growth factor-beta1 (TGF-B1) is a tumor suppressor in normal and early stage prostate cancer (PCa) cells, but exerts pro-tumorigenic effects during progression to metastatic disease, and correlates with poor prognosis. However, the mechanisms whereby TGF-B1 induces pro-metastatic action are uknown. Previously it was reported that the LNCaP cell line was insensitive to TGF-B-mediated growth suppression. Thus we sought to examine the TGF-B1-induced proliferative response of increasingly metastatic, lineage-related LNCaP sublines. Under reduced serum conditions we show that TGF-B1 inhibits cell proliferation profoundly and promotes apoptosis in castrate-insensitive LNCaP sublines, whereas inhibition of cell proliferation is marginal in LNCaP cells. Growth inhibitory effects and apoptosis are mediated by active TGF-B receptors, TBRII and TBRI, and the downstream Smad2/3 effectors. Knock down of TBRII with a dominant negative construct, as well as inhibition of kinase activity abrogrates these effects. Additionally, we show that TGF-B enhances cytoskeletal rearrangements and increases motility on selected extracellular matrices in metastatic LNCaP sublines. TGF-B signaling in castrate-resistant PCa cell lines is more robust than in hormonally sensitive clones and leads to selective activation of cell motilty that influences PCa cell metastatic behavior with potential consequences for bone colonization. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3184.
AB0489 Serum chemokines in rheumatoid arthritis patients treated with repeated infusions of infliximab
Authors: P.A. Klimiuk, S. Sierakowski, I. Domyslawska, J. Chwiecko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chemokines have an important role in the infiltrating of rheumatoid synovium with mononuclear cells, leading to the initiation and progression of the rheumatoid arthritis (RA). <h3>Objectives</h3> We studied the effects of the multiple infusions of infliximab, a chimeric anti-tumor necrosis factor alpha (anti-TNF-α) antibody, on the serum chemokines levels in patients with active RA. <h3>Methods</h3> RA patients were supposed to receive 9 infusions of infliximab (3mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter with the same dose. All patients continued treatment with methotrexate (MTX) (7.5-20mg/week). Serum concentrations of interleukin-8 (IL-8), RANTES (regulated upon activation, normal T cell expressed and secreted) and monocyte chemoattractant protein-1 (MCP-1) were assessed by ELISA on weeks 0, 2, 6, 14, 38, prior to infusion, and additionally on week 62. <h3>Results</h3> Initial infusion of infliximab caused reduction in serum IL-8, RANTES and MCP-1 (in all cases p&lt;0.001) levels. Subsequent infliximab administrations also significantly decreased serum chemokines levels, but was less effective. Prior to the first infliximab infusion serum concentrations of studied chemokines correlated with markers of RA activity such as the erythrocyte sedimentation rate (ESR) or CRP levels, number of swollen joints and disease activity score (DAS). Following next drug infusions such associations were far less significant. Infliximab treatment induced a significant reduction in the number of monocytes observed through the whole study (in all cases p&lt;0.05). <h3>Conclusions</h3> Anti-TNF-α antibody therapy accompanied by MTX, beside a rapid clinical improvement, reduced serum chemokines concentrations in RA patients. Subsequent administrations of infliximab sustained chemokines decrease, although to a lesser extent than the first two doses of infliximab. <h3>Disclosure of Interest</h3> None Declared
Primary and Secondary Syphilis
Authors: Michael P Schön, Hans P Bertsch
Journal: New England Journal of Medicine (2016)

A previously healthy 68-year-old man presented with a solid erosive sore on the inside of his upper lip. He also had sharply demarcated erythematous, scaly plaques on his hands and feet, including the palms and soles. The lesions had been present for over a year.
Abstract 3114: Constitutively active signal transducer and activator of transcription-3: an oncogene that increases gap junctional intercellular communication.
Authors: Aaron Trotman-Grant, Mulu Geletu, Leda Raptis
Journal: Cancer Research (2013)

Abstract Gap junctions are specialized intercellular channels that connect the cytoplasm of adjacent cells and mediate the direct exchange of small ions and molecules between them. Gap junctional intercellular communication (GJIC) is usually blocked, or downregulated, in cells transformed by oncogenes, such as Src. One of the Src effector pathways leading to transformation and GJIC suppression is the Ras/Raf/MEK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway that has a prominent etiological role in cell proliferation, differentiation and cell survival; inhibition of this pathway in vSrc transformed cells restores GJIC. In addition, the distinct downstream effector of Src that is obligatory for neoplasia is the signal transducer and activator of transcription-3 (Stat3). Stat3 has the intrinsic characteristic of being upregulated in a range of tumors, and a modified version, the constitutively active form of Stat3 (Stat3C), has been shown to function as an oncogene. Conversely, inhibition of Stat3 can suppress tumor growth. To examine the role of Stat3 upon the Src-mediated, GJIC suppression, Stat3 was downregulated in rat liver epithelial T51B cells expressing activated Src through treatment with the CPA7, Stat3 inhibitor, or through infection with a retroviral vector expressing a Stat3-specific shRNA. The extent of GJIC was determined by electroporating the fluorescent dye, Lucifer yellow, into cells grown on two co-planar electrodes of electrically conductive, optically transparent, indium-tin oxide, followed by observation of the migration of the dye to the adjacent, non-electroporated cells under fluorescence illumination. The results demonstrate that, contrary to inhibition of the Ras pathway, Stat3 inhibition in cells expressing activated Src does not restore GJIC. On the contrary, Stat3 inhibition in normal cells with high GJIC levels eliminated junctional permeability. Interestingly, our results also demonstrate that expression of Stat3C in T51B cells and human lung cancer SK-LuCi6 cells, which have extensive communication and low Src levels, increased GJIC. Therefore Stat3, although it is generally growth promoting and in an activated form can act as an oncogene, its function is actually required for and increases junctional permeability. Citation Format: Aaron Trotman-Grant, Mulu Geletu, Leda Raptis. Constitutively active signal transducer and activator of transcription-3: an oncogene that increases gap junctional intercellular communication. [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 3114. doi:10.1158/1538-7445.AM2013-3114
Abstract 4349: The chromosome 17q oncogene LASP1 promotes metastatic dissemination of medulloblastoma
Authors: Marc Remke, Christopher Traenka, Andrey Korshunov, Sebastian Bender, Hendrik Witt, Paul A. Northcott, Wolfram Scheurlen, Guido Reifenberger, Michael D. Taylor, Andreas E. Kulozik, Peter Lichter, Elke Butt, Stefan Pfister
Journal: Cancer Research (2010)

Abstract Medulloblastoma is the most common malignant brain tumor and one of the leading causes of cancer-related mortality in children. Treatment failure mainly occurs in children harboring tumors with microscopic or macroscopic metastases at the time of diagnosis, which typically show gain of 17q (often based on an isochromosome 17q), a common cytogenetic hallmark of intermediate and high-risk medulloblastoma. To pinpoint the oncogene(s) targeted by 17q gain, mRNA expression profiling was carried out in primary tumors with and without this indicative aberration and identified LIM and SH3 protein 1 (LASP1) as one of the most up-regulated genes on chromosome 17q in tumors with 17q gain. LASP1 (earlier named MLN50) was initially identified from a cDNA library of nodal breast cancer metastases and is highly expressed in more than 50% of metastatic human breast cancer, ovarian cancer, and hepatocellular carcinoma. In our study in medulloblastoma, a strong association of LASP1 mRNA abundance with 17q gain and metastatic disease at diagnosis was confirmed by quantitative real-time PCR in an independent cohort of 101 primary tumor samples. Protein expression was analyzed by immunohistochemistry in a large cohort of patients (n=207). High LASP1 protein expression was found to be strongly correlated with 17q gain, metastatic dissemination, and inferior overall and progression-free survival confirming our results on transcript level. Furthermore, multivariate analyses revealed LASP1 protein expression as an independent novel prognostic marker for overall survival and tumor progression in medulloblastoma. In vitro experiments in three established medulloblastoma cell lines demonstrate a strong reduction of cell migration and decreased proliferation upon LASP1 knockdown via siRNA, further indicating a functional role for LASP1 in the progression and metastatic dissemination of medulloblastoma. In conclusion, we have identified LASP1 as an important player in the metastatic dissemination of medulloblastoma which additionally has a high potential to serve as a molecular biomarker for outcome prediction in future prospective studies. Furthermore, LASP1 comprises a promising novel candidate molecule for future targeted therapy approaches in high-risk medulloblastoma. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4349.