tbuckley/cabot-search huggingface dataset:
SHOULD A VISIT TO THE RADIOLOGY DEPARTMENT BE THE FIRST STEP IN THE DIAGNOSIS OF ACTIVE INFLAMMATORY BOWEL DISEASE?
Authors: M Cotter, B Christopher, S Jadhav, S Sengupta, J Keohane
Journal: Gut (2013)

<h3>Introduction</h3> CT is the most commonly used method of imaging in the diagnosis and management of Inflammatory Bowel Disease. However, for those patients admitted with typical symptoms, does imaging accurately identify Crohn9s Disease (CD) and Ulcerative Colitis (UC) prior to direct visualisation and histological diagnosis at endoscopy? <h3>Aims/Background</h3> To assess the correlation between the findings of contrast CT (abdomen or enteroclysis) and colonoscopy results in patients with a suspected diagnosis of IBD. <h3>Method</h3> A retrospective study was performed on 27 patients between September 2009 and January 2013, the majority of whom had been referred for endoscopy to confirm the results of their initial CT. Histopathological results and macroscopic findings at colonoscopy were compared to features of active inflammation as noted on contrast CT. <h3>Results</h3> There were 19 female and 8 male subjects. The average age at time of CT was 51 (female) and 32 (male) with a range of 19 to 86 years. The most common clinical indication for performing CT was abdominal pain (74%). Of note, 21 patients had a plain film of abdomen prior to CT, 19 of which were reported normal. Ct enteroclysis was performed on 4 patients. 27 patients had CT findings suggestive of IBD on CT whereas only 17 (63%) had confirmed CD or UC at endoscopy. <h3>Conclusion</h3> This study suggests that in a cohort of patients likely to be exposed to high doses of radiation, such as those with IBD, a visit to the endoscopy room could be more worthwhile in their initial diagnosis.
AB0374 Influence of body composition and abdominal adiposity on endothelial dysfunction and radiological damage in patients with rheumatoid arthritis
Authors: E. Delgado-Frías, I. Ferraz-Amaro, M. Flores-Rodríguez, J. Viotti, C. Rodríguez de la Rosa, V. Hernández-Hernández, M. Arce-Franco, M. Gantes, J. Muñiz, M. Dominguez-Luis, A. Herrera-García, A. Rodríguez-Vargas, M. Gonzalez-Diaz, M. Gomez-Rodríguez-Bethencourt, F. Diaz-Gonzalez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To explore the influence of body composition and abdominal adiposity on endothelial dysfunction and radiological damage in Rheumatoid Arthritis (RA) patients. <h3>Methods</h3> A total of 100 patients, 54 RA patients and 46 controls, adjusted for sex, body mass index (BMI), age and comorbidity, were included. Total body composition was measured by dual energy X-ray absorptiometry; total and regional lean mass, fat mass, fat free mass index (fat free mass/m<sup>2</sup>) and fat mass index (fat mass/m<sup>2</sup>) were established. Quantification of visceral and parietal abdominal fat area was determined using magnetic resonance imaging, as well as visceral/parietal fat index. Endothelial dysfunction was assessed by brachial artery flow-mediated dilatation (FMD) as the dilator response to 5 minutes distal cuff occlusion and after sublingual nitroglycerine administration, and the Sharp Score defined radiological damage. The 28-joint DAS (DAS-28) and disability using HAQ (Health Assessment Questionnaire) scores, erythrocyte sedimentation rate (ESR) and C-reactive protein were collected. Multivariate analysis was performed to compare body composition between controls and patients and the relationship between those and endothelial dysfunction and radiological damage, everything adjusted for demographic and comorbidity variables. <h3>Results</h3> In the univariate analysis RA patients showed less flow-mediated dilatation (5.9 vs 9.8 mm, p=0.03). Similarly, fat free mass index was higher in patients than in controls (beta coefficient 0,94 (CI95% 0,08-1,80), P=0,03) after adjusting for BMI, sex and age; on the other hand fat mass index tended to be higher in patients than in controls (beta coefficient 2,51 (CI95% -0,82-5,84), p=0.13). Parietal and visceral abdominal fat values did not show differences between controls and patients. Fat mass, lean mass and abdominal fat did not correlate with DAS-28, HAQ, ESR or CRP. Parietal abdominal fat through resonance imaging in RA patients showed a negative relation with flow-mediated dilatation (beta coefficient -0.045 mm FMD/cm<sup>2</sup> parietal area, p=0.02) after adjusting for BMI. This relation was not found with visceral abdominal fat. Radiological damage was negatively correlated with total bone mass (beta coefficient -1,13, CI95% -2,05-0,22, p=0.02) and showed a negative trend to do it also with total lean mass (beta coefficient -1.11 CI95% 2,42-0,21, p=0,09). <h3>Conclusions</h3> Changes in body composition take place in RA patients. These changes can be related to the endothelial dysfunction and radiological damage that occurs in this disease. <h3>Disclosure of Interest</h3> None Declared
Prevalence of and treatment outcomes for patients with obstructive sleep apnoea identified by preoperative screening compared with clinician referrals
Authors: Akshay Dwarakanath, Vinod Palissery, Mark W. Elliott
Journal: European Respiratory Journal (2016)

Obstructive sleep apnoea (OSA) has implications perioperatively. We compared the prevalence of OSA and outcome with continuous positive airway pressure (CPAP) in patients diagnosed through preoperative screening and following referrals from other clinicians. Among 1412 patients (62% males) the prevalence of OSA, Epworth Sleepiness Score (ESS), the number referred for CPAP, and short and longer term use of CPAP were compared between the two groups. The prevalence of OSA was similar (62% versus 58%). There were differences in mean± sd age (61±16 versus 55±13 years; p&lt;0.0001), ESS (11±6 versus 8±5; p&lt;0.0001) and oxygen desaturation index (22±20 versus 19±17; p=0.039). Clinician-referred patients were more likely to be offered CPAP (p&lt;0.0001; OR 2.84). Pre-assessment patients with mild OSA were less likely to continue CPAP long term (p=0.002; OR 6.8). No difference was seen between moderate and severe OSA patients. The prevalence of OSA was similar in both groups but pre-assessment patients were younger and less symptomatic. Preoperative screening of patients is worthwhile, independent of any effect of CPAP upon surgical outcomes; younger and less symptomatic patients are identified earlier. Pre-assessment patients with mild OSA were less likely to use CPAP; this should be considered when offering CPAP to these patients prior to surgery.
Genetic Defects of Intracellular-Membrane Transport
Authors: Vesa M. Olkkonen, Elina Ikonen
Journal: New England Journal of Medicine (2000)

The compartmentalization of functions into distinct membrane-bound organelles is a central characteristic of cells. The protein and lipid composition of these organelles is unique, a factor that is vital for their proper function. This necessitates tightly controlled transport of biomolecules from their sites of synthesis or uptake to specific destinations, and mechanisms that prevent promiscuous interactions between cellular membranes that would lead to deleterious mixing of organelle constituents. One of the major processes responsible for the correct localization of molecules within the cell is called membrane or vesicular transport. In this process, membranous carrier structures bud off a donor compartment . . .
Abstract LB-81: SHARE'S Achievements
Authors: Deborah Polinsky
Journal: Cancer Research (2011)

Abstract SHARE's mission is to create and sustain a supportive community of women affected by breast or ovarian cancer in which survivors provide their experiences to newly-diagnosed women, their families and their friends. SHARE enables participants with the opportunity to receive and exchange information, support, strength, and hope. The organization's work focuses on patient empowerment, personal and community education, and public policy advocacy to bring about an improved quality of life, better heath care, and a cure for these diseases. For nearly thirty-five years SHARE has been providing peer support services and the latest research findings. SHARE is now an international organization which annually helps over 20,000 women and men affected by breast or ovarian cancer. It has helped establish similar affiliate programs around the United States and in Russia, the Ukraine, Bosnia, Poland and Israel. 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 LB-81. doi:10.1158/1538-7445.AM2011-LB-81
Transmission of Multidrug-Resistant<i>Mycobacterium tuberculosis</i>during a Long Airplane Flight
Authors: Thomas A. Kenyon, Sarah E. Valway, Walter W. Ihle, Ida M. Onorato, Kenneth G. Castro
Journal: New England Journal of Medicine (1996)

In April 1994, a passenger with infectious multi-drug resistant tuberculosis traveled on commercial-airline flights from Honolulu to Chicago and from Chicago to Baltimore and returned one month later. We sought to determine whether she had infected any of her contacts on this extensive trip.Passengers and crew were identified from airline records and were notified of their exposure, asked to complete a questionnaire, and screened by tuberculin skin tests.Of the 925 people on the airplanes, 802 (86.7 percent) responded. All 11 contacts with positive tuberculin skin tests who were on the April flights and 2 of 3 contacts with positive tests who were on the Baltimore-to-Chicago flight in May had other risk factors for tuberculosis. More contacts on the final, 8.75-hour flight from Chicago to Honolulu had positive skin tests than those on the other three flights (6 percent, as compared with 2.3, 3.8, and 2.8 percent). Of 15 contacts with positive tests on the May flight from Chicago to Honolulu, 6 (4 with skin-test conversion) had no other risk factors; all 6 had sat in the same section of the plane as the index patient (P=0.001). Passengers seated within two rows of the index patient were more likely to have positive tuberculin skin tests than those in the rest of the section (4 of 13, or 30.8 percent, vs. 2 of 55, or 3.6 percent; rate ratio, 8.5; 95 percent confidence interval, 1.7 to 41.3; P=0.01).The transmission of Mycobacterium tuberculosis that we describe aboard a commercial aircraft involved a highly infectious passenger, a long flight, and close proximity of contacts to the index patient.
SP0072 The Application of Diagnostic Ultrasound to the Management of Inflammatory Arthritis: A Foot &amp; Ankle Perspective
Authors: L. S. Hooper
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Understanding of the real world uses of diagnostic ultrasound (US) within rheumatological practice has grown significantly in recent years. Consequently, the use of US is also expanding to include assessment of the foot and ankle. Early studies of disease activity and progression have demonstrated that the foot can respond slower and inadequately to many routine therapeutic approaches and there remains an unmet burden of foot disease within our inflammatory arthritis populations. US offers a potentially readily available, chair-side aid to foot and ankle assessment, influencing clinical decision making practices. This session therefore seeks to highlight the current concepts, challenges and future potential regarding the use of diagnostic ultrasound for the management of foot and ankle pathology in patients with inflammatory arthritis. <h3>Disclosure of Interest</h3> None Declared
Esophageal Duplication Cyst
Authors: Ahmed Abu-Zaid, Ayman Azzam
Journal: New England Journal of Medicine (2014)

An otherwise healthy 23-year-old man presented with a 3-week history of difficulty swallowing solid food and associated vomiting. He reported no history of respiratory symptoms or weight loss. A barium-swallow examination showed substantial luminal narrowing of the distal esophagus (Panel A, arrows), and a focal mass effect could be seen anteriorly on a second projection (Panel B, arrows). Computed tomography (CT) of the chest performed after the administration of contrast material showed a well-defined, bilobed, cystic mediastinal mass measuring 7.3 cm by 3.2 cm by 7.0 cm. The mass was contiguous with the distal esophagus (Panel C, white arrows), which . . .
FRI0273 Reactivation of Hepatitis B Virus in Patients Treated with Anti-TNF Therapy
Authors: S.M. Jung, J.Y. Kang, H.K. Min, J.H. Koh, Y.S. Suh, J.H. Lee, J. Lee, J.Y. Lee, J.-M. Kim, S.-K. Kwok, J.H. Ju, K.-S. Park, H.-Y. Kim, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Anti-TNF therapy was known to increase the risk of certain infection. There are no sufficient data about the reactivation of hepatitis B virus (HBV) after anti-TNF therapy. <h3>Objectives</h3> The study was aimed to investigate the clinical course of hepatitis B in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) after the introduction of anti-TNF therapy. <h3>Methods</h3> We retrospectively reviewed to identify patients infected with HBV treated with TNF inhibitors between October, 2004 and September, 2013. For patients with HBV infection, the liver enzyme and the viral status were monitored. The HBV reactivation was defined according to the Korean guideline by hepatology. <h3>Results</h3> Of 983 patients (RA, n=536; AS, n=447) who were treated with TNF inhibitors, 23 patients (RA, n=17; AS, n=6) had comorbidities of HBV infection. Eighteen patients were treated with etanercept, three with adalimumab, and two with infliximab. Seven patients received pre-emptive antiviral prophylaxis before anti-TNF therapy: 4 with entecavir, 1 with telbivudine, 1 with tenofovir, and 1 with lamivudine. Among 23 patients with HBV infection, 4 (17.4%) patients experienced the reactivation of HBV, which occurred in 3 patients without prophylaxis and 1 patient with lamivudine prophylaxis. In the latter case, YMDD mutation was identified and addition of adefovir resulted in virological response. The other three patients were treated successfully with entecavir or tenofovir. There was no subsequent events associated with HBV infection. <h3>Conclusions</h3> This study indicates the risk of HBV reactivation after anti-TNF therapy. Careful management is mandatory for patients who planned to be treated with TNF inhibitors. <h3>References</h3> Vassilopoulos D, Calabrese LH. Management of rheumatic disease with comorbid HBV or HCV infection. Nature reviews Rheumatology. 2012 Jun;8(6):348-57 Oketani M, Ido A, Uto H, Tsubouchi H. Prevention of hepatitis B virus reactivation in patients receiving immunosuppressive therapy or chemotherapy. Hepatology research: the official journal of the Japan Society of Hepatology. 2012 Jul;42(7):627-36 Korean Association for the Study of the L. KASL Clinical Practice Guidelines: Management of chronic hepatitis B. Clinical and molecular hepatology. 2012 Jun;18(2):109-62 <h3>Acknowledgements</h3> This study was supported by a grant from the Korea Healthcare Technology R&amp;D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5251
Adiponectin activates tumor suppressor LKB1 and AMP-activated protein kinase signaling to inhibit malignant properties of breast cancer cells.
Authors: LT Smith, BB Knight, NK Saxena, D Sharma
Journal: Cancer Research (2009)

Abstract Abstract #3067 Introduction: The prevalence of obesity in the developed world has reached epidemic proportions in recent years. Obese breast cancer patients exhibit a higher risk for metastasis, larger tumor burden and poorer response to endocrine therapy. Therefore, it is very important to understand the adverse effects of obesity on breast cancer in order to devise appropriate new approaches to their treatment. Obesity is considered an endocrine disorder and serum levels of adiponectin, an adipocytokine proposed to have therapeutic potential, get significantly lowered with obesity. More recently, low serum adiponectin levels were associated with increased risk and more aggressive phenotype (larger tumor size and high histological grade) of breast cancer in women. Recently, anti-proliferative and pro-apoptotic response of adiponectin was shown in breast cancer cells but the molecular mechanisms governing the anti-cancer effects of adiponectin largely remain unknown. In the present study, we found a novel mechanism underlying adiponectin action involving upregulation of tumor suppressor LKB1 and activation of AMPK (AMP-activated protein kinase) signaling to inhibit malignant properties of breast cancer cells.&amp;#x2028; Methods and Results: Adiponectin inhibited malignant properties such as invasion and migration of breast cancer cells in matrigel invasion, scratch migration and quantitative Electric Cell-Substrate Impedance Sensing (ECIS) invasion and migration assays. Interestingly, adiponectin induced phosphorylation of AMPK at Thr 172 in breast cancer cells. Adiponectin treatment also affected downstream targets of mTOR signaling pathway, including decreased phosphorylation of p70S6K showing the involvement of mTOR-S6K axis. Intriguingly, we found that adiponectin increased the expression of tumor suppressor LKB1 in breast cancer cells. Co-immunoprecipitation assays revealed that LKB1 co-immunoprecipitated with tumor suppressor TSC2. Increase in expression of upstream kinase LKB1 might directly regulate adiponectin induced activation of AMPK. We also found that breast cancer cells transfected with wild-type LKB1 plasmids increased phosphorylation of AMPK and decreased phosphorylation of p70S6K showing decrease in mTOR activity. In contrast, breast cancer cells transfected with kinase dead LKB1 decreased phosphorylation of AMPK and increased activation of p70S6K.&amp;#x2028; Discussion: Taken together these data indicate a novel crosstalk between adiponectin and tumor suppressor LKB1 that modulates AMPK-S6K axis and inhibits metastatic properties, invasion and migration of breast cancer cells. The influence of adipocytokine, adiponectin on breast carcinogenesis is just beginning to be elucidated and our study is the first to show the direct involvement of tumor suppressor genes LKB1 and TSC2 in anti-cancer effects of adiponectin. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3067.
Abstract 4375: Hrk mediates 2-methoxyestradiol-induced mitochondrial apoptotic signaling in prostate cancer cells.
Authors: Inik Chang, Shahana Majid, Sharanjot Saini, Mohd S. Zaman, Soichiro Yamamura, Takeshi Chiyomaru, Varahram Shahryari, Shinichiro Fukuhara, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2013)

Abstract Prostate cancer is one of the most prevalent cancers in males and ranks the second most common cause of cancer related deaths. 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, is a promising anticancer agent for various types of cancers. Although 2-ME has been shown to activate Jun N-terminal kinase (JNK) and mitochondrial dependent apoptotic signaling pathways, the underlying mechanisms including downstream effectors remain unclear. Here, we report that the human Bcl-2 homology 3 (BH3)-only protein harakiri (Hrk) is a critical effector of 2-ME-induced-JNK dependent apoptosis in prostate cancer cells. Hrk mRNA and protein are preferentially up-regulated by 2-ME, and Hrk induction is dependent on JNK activation of c-Jun. Hrk knockdown prevents 2-ME-mediated apoptosis by attenuating the decrease in mitochondrial membrane potential, subsequent cytochrome c (cyt c) release and caspase activation. Conversely, Hrk over-expression increases caspase-dependent prostate cancer cell apoptosis. Involvement of the pro-apoptotic protein Bak in this process suggested the possible interaction between Hrk and Bak. Thus, Hrk activation by 2-ME or its over-expression displaced Bak from the complex with anti-apoptotic protein Bcl-xL, while deletion of the Hrk BH3 domain abolished its interaction with Bcl-xL, reducing the pro-apoptotic function of Hrk. Finally, Hrk is also involved in the 2-ME-mediated reduction of X-linked inhibitor of apoptosis (XIAP) through Bak activation in prostate cancer cells. Together, our findings suggest that induction of the BH3-only protein Hrk is a critical step in 2-ME activation of the JNK-induced apoptotic pathway targeting mitochondria by liberating pro-apoptotic protein Bak. Citation Format: Inik Chang, Shahana Majid, Sharanjot Saini, Mohd S. Zaman, Soichiro Yamamura, Takeshi Chiyomaru, Varahram Shahryari, Shinichiro Fukuhara, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Hrk mediates 2-methoxyestradiol-induced mitochondrial apoptotic signaling in prostate cancer cells. [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 4375. doi:10.1158/1538-7445.AM2013-4375
P1098 : Influence of metabolic risk factors in hepatotoxicity (DILI) phenotype and outcome
Authors: M. Robles-Díaz, I. Medina-Cáliz, A. Ruíz, J. Sanabria, C. Stephens, A. González-Jiménez, A. Ortega-Alonso, B. García-Muñoz, M. García-Cortés, M. Romero-Gómez, G. Peláez, H. Hallal, G. Soriano, E. Román, S. Blanco, A. Castiella, E.M. Zapata, J.M. Navarro, M. Jiménez, J.M. Moreno-Planas, A. Aldea, F. Bessone, N. Hernández, M. Arrese, M.I. Lucena, R.J. Andrade
Journal: Journal of Hepatology (2015)
Abstract 4788: Protein kinase CK2 modulates TAp73 phosphorylation and suppresses apoptosis in head and neck cancer
Authors: Hai Lu, Matthew Brown, Michael Hu, Gretchen Unger, Carter Van Waes, Zhong Chen
Journal: Cancer Research (2011)

Abstract The TP53 family member TAp73 has been shown to be pro-apoptotic and enhance chemosensitivity, but is inactivated in head and neck squamous cell carcinoma (HNSCC). We recently found that the inflammatory cytokine, TNFα, induces NF-κB activation and TAp73 nuclear export, which contribute to the suppression of TAp73 pro-apoptotic function. However, the intermediate signaling involved in TNFα regulated TAp73 inactivation and modulation of apoptosis has not been defined. Here, we found that TAp73 exhibits varying levels of phosphorylation in a panel of HNSCC cell lines. An inverse association between phospho- and total TAp73 protein expression was observed, suggesting that signal phosphorylation could contribute to TAp73 turnover. In response to TNFα treatment, phosphorylated TAp73 decreased in the nucleus while increasing in the cytoplasm, consistent with nuclear-cytoplasmic translocation. As we previously showed that protein kinase CK2 subunits are aberrantly overexpressed and promote IKK-NF-κB activation in HNSCC, we examined CK2 as a potential upstream regulator of TAp73 phosphorylation. Both CK2 inhibitor DMAT (2-Dimethy-lamino-4,5,6,7-tetrabromo-1H-benzimidazole) and CK2α siRNA inhibited TAp73 phosphorylation, as well as increased TAp73 mRNA and protein expression. Consequently, DMAT treatment increased the expression of TAp73 downstream pro-apoptotic genes, p21, PUMA and NOXA through increased TAp73 binding to the promoters of these genes. DMAT treatment and mutation of TAp73 phosphorylation sites increased p21 reporter activity. Furthermore, DMAT blocked cell cycle progression and proliferation, and increased apoptosis of HNSCC in vitro. Delivery of anti-CK2α/α′ oligodeoxy-nucleotide nanocapsules into HNSCC xenograft models significantly suppressed tumor growth, concomitant with decreased TAp73 phosphorylation, increased expression of TAp73, and target apoptotic proteins PUMA and NOXA. These results suggest that the aberrant activation of protein kinase CK2 could be one of the upstream signaling molecules modulating phosphorylation of TAp73, TAp73 nuclear exportation, and suppression of apoptosis in HNSCC cells. 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 4788. doi:10.1158/1538-7445.AM2011-4788