tbuckley/cabot-search huggingface dataset:
PMO-139 Human cytomegalovirus infection of human hepatic sinusoidal endothelial cells promotes CD4 T cell adhesion and transmigration
Authors: T Bruns, A Pachnio, P F Lalor, P A Moss, D H Adams
Journal: Gut (2012)

<h3>Introduction</h3> Animal studies suggest that sinusoidal endothelial cells and not hepatocytes are the site of cytomegalovirus (CMV) latency and reactivation in the liver and the source of secondary viral spread. Furthermore, murine CMV infection of sinusoidal endothelium is able to break immunotolerance and induce a strong T cell effector response. The aim of this study was to investigate, whether CMV infection of human hepatic sinusoidal endothelial cells (HSEC) modulates the ability of the liver to recruit and activate lymphocyte. <h3>Methods</h3> Recombinant endotheliotropic eGFP-labelled CMV was propagated in RPE-1 cells and purified by ultracentrifugation in tartrate/glycerol gradients. Primary HSEC were isolated from explanted livers, grown to confluence and infected with CMV over 2 h. Infection was confirmed by fluorescence microscopy and plaque assay on fibroblasts. Chemokines and adhesion molecules were quantified by ELISA. Isolated primary lymphocytes and CMV-specific CD4 T cell clones were perfused over HSEC monolayers under constant flow simulating physiological shear stress and adhesion and transmigration recorded using phase contrast microscopy. Trans-well assays were used to study the phenotype of transmigrated cells using flow cytometry. <h3>Results</h3> Human sinusoidal endothelial cells were permissive to CMV infection. CMV infection induced secretion of CXCL10 and CCL5 as well as an up-regulation of VCAM-1 and ICAM-1 surface expression. Early CMV infection resulted in a fourfold increase in the adhesion of allogeneic lymphocytes to infected HSEC monolayers compared with mock-infected endothelium. Under flow, transendothelial migration of CMV-reactive CD4 T cell clones was increased through CMV-infected endothelium and could be significantly reduced by the use of anti-CXCL10 antibodies. Transmigrated allogeneic CD4 CD45RO+ T cells and CMV-reactive T cell clones displayed increased expression of the early activation marker CD69 after transendothelial migration through CMV-infected HSEC. <h3>Conclusion</h3> CMV infection of HSEC facilitates the up-regulation of cell-adhesion molecules and chemokines resulting in increased adhesion, transmigration and activation of CD4 T cells. This may explain how human CMV infection not only provokes significant hepatitis but also increases hepatic immune activation in graft rejection. <h3>Competing interests</h3> None declared.
Abstract 852: Prognostic value of circulating endothelial and progenitor cells in advanced cancer patients enrolled in phase 1 in association with clinical prognostic scores
Authors: Christophe Massard, Marie-Cecile Le Deley, Carlos Gomez Roca, Isabelle Borget, Jean-Charles Soria, Françoise Farace
Journal: Cancer Research (2010)

Abstract Background New surrogate biomarkers such as circulating endothelial cell (CEC) and progenitor cell (CEP) have been proposed to monitor anti-vascular drug activity. During anti-angiogenic therapy, dramatic changes in both CEC and CEP levels were observed. Moreover, these biomarkers may also be used as a candidate prognostic and predictive biomarker in patients with advanced cancer. Methods Medical charts of patients treated in one centre and enrolled into five Phase I trials with anti-vascular therapies between October 2005 and April 2009 were reviewed for clinical characteristics and validated clinical prognostic factors (albumin, lactate dehydrogenase, number of metastatic sites)(Arkenau et al, JCO 2009). Overall 70 patients had CEC or CEP evaluation at baseline. CECs were measured in one ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45-CD31+CD146+ 7-amino-actinomycin (7AAD)- phenotype… CEPs were measured in 10ml blood after progenitor cell enrichment and were identified by FCM as extremely rare events with a CD45dimCD34+VEGFR2+7AAD- phenotype. We studied the impact of CEC and CEP values on the overall survival (OS) adjusted on the clinical prognostic score. Results The median age was 50 years (range, 21 to 78 years). Median baseline CEC value was 12/ml (range, 0 to 154). The CEPs were measured in 57 patients; the median CEP value was 1.3% of hematopoietic stem cells, with range from 0% to 32.5% (absolute counts: 12/ml, range, 0 to 392/ml). 31/57 had CEP values greater than 1% of HSC. Median follow-up was 23 months. The risk of death was significantly increased in patients with prognostic score greater than 0 as compared to patients with score equal to 0 (Median OS 9.2 versus 24.2 respectively) as well as in patients with increased CEP (&amp;gt;1%) as compared to those with lower values (Median OS 9.0 versus 13.3). Both factors remained significant in multivariate analysis (HR=3.9, 95%CI, 0.95-16.6, p=0.02 and HR=2.1, 95%CI, 1.0-4.3, p=0.04, respectively). We did not observe any relationship between the CEC level and the outcome. Conclusion This analysis suggests that a prognostic score based on CEP level combined with clinical characteristics could be a helpful tool to determine the prognosis of patients with advanced cancers enrolled into phase 1 trials. Further studies are requested to confirm these findings. 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 852.
P48 Should chronic obstructive pulmonary disease be a contra-indication to blocker prescription in patients with concomitant heart failure?
Authors: D. C. Lees, M. Simpson, E. McKay, S. J. Owen
Journal: Thorax (2011)

<h3>Introduction</h3> Beta blockers (BB) are now well established in the treatment of heart failure (HF) and other cardiovascular disorders. There is much debate in the literature as to their safety in patients with concomitant chronic obstructive pulmonary disease (COPD) due to the risk of increased symptoms and decline of FEV<sub>1</sub>. As BB use improves morbidity and mortality in CVD are we justified in denying this benefit to patients with co-existing COPD? <h3>Objective</h3> To ask cardiologists within our Deanery about their prescribing preferences for BB in patients with both HF and COPD and any adverse events they had experienced as a result of those prescriptions. <h3>Method</h3> Four questions were sent out to 50 consultant cardiologists and 20 registrars asking BB of choice with adverse events experienced or reasons to avoid them. <h3>Results</h3> 30/50 Consultants responded with 7/20 registrar responses. 100% prescribed BB to patient with COPD and HF with only 6 (16%) responders describing adverse outcomes. These included increasing shortness of breath (6/37), wheeze (6/37) and bronchospasm (1/37). The most commonly prescribed BB was bisoprolol (89%), followed by nebivolol (40%), carvedilol (37%) and metoprolol (21%). <h3>Conclusion</h3> Our results show that a diagnosis of COPD is not considered a contraindication to BB prescription by cardiologists with few reporting an increase in symptoms. We would suggest that all patients with COPD and HF should at least be considered for BB therapy while being mindful of potential adverse effects.
Pseudoaneurysm and Coronary Abscess Secondary to Coronary Stent Fracture Identified With Tc-99m Hexamethylpropyleneamine Oxime-Labeled White Blood Cell SPECT/CT Scintigraphy
Authors: Kelvin S H Loke, H Y Loi, Anthony S W Goh, David C E Ng
Journal: Clinical Nuclear Medicine (2011)

A radionuclide Tc-99m hexamethylpropyleneamine oxime white blood cell scan with SPECT/CT was requested for the investigation of pyrexia and bacteraemia in a 69-year-old gentleman who was status postcoronary angiography and stenting. Abnormal radiotracer activity in the region of the left anterior descending artery was observed, which on subsequent histopathology found to be a pseudoaneurysm and coronary abscess.
Abstract 5541: Therapeutic targeting of CRM1 in ovarian cancer.
Authors: Takahito M. Miyake, Sunila Pradeep, Behrouz Zand, Heather J. Dalton, Yunfei Wen, Guillermo N. Armaitz Pena, Michael Kauffman, Dilara McCauley, Sharon Shacham, John E. Wiktorowicz, Anil K. Sood
Journal: Cancer Research (2013)

Abstract Background: CRM1 is a nuclear export protein which increases cell viability through nuclear export signal-dependent protein exclusion of tumor suppressor proteins. Selective Inhibitor of Nuclear Exprot (SINE) is a novel class of drugs that selectively inhibit CRM1. Here, we tested the biological effects of targeting CRM1. Methods and results: To explore the efficacy of SINE CRM1 anatgonists in ovarian cancer, we tested the selective small molecule KPT-185(in vitro) against human ovarian cancer cell lines. KPT-185 reduced cell viability in multiple (A2780, A2780CP20, IGROV-1 and SKOV3) human ovarian cancer cell lines with IC50 levels ranging from 0.2 - 0.75μM. Nuclear localization and significantly increased expression of tumor suppressor proteins (e.g., p53, p21 and Fox03a) was noted in response to KPT-185 treatment. Moreover, synergistic reduction in cell viability was noted with topotecan, cisplatin and liposomal doxorubicin (interaction index was 0.45, 0.78 and 0.59, respectively). Using the A2780 in vivo orthotopic ovarian cancer model, oral administration of KPT-330 (in vivo) monotherapy at 20mg/kg twice a week resulted in 90% tumor reduction (p&amp;lt;0.01). In combination with topotecan, there was 98% reduction (p&amp;lt;0.01) in tumor growth. KPT-330 also showed significant tumor growth inhibition in combination with weekly paclitaxel or bevacizumab. Histological examination of obtained tumor samples showed 2.5-fold increase in number of caspase-3 positive cells (p&amp;lt;0.01) and 0.4-fold decreased of Ki67 positive cells (p&amp;lt;0.05) in KPT-330 treated group. In each experiment, KPT-330 was well tolerated and no significant changes in mouse body weight were noted. Conclusion: CRM1 inhibitor is a potent inhibitor of ovarian cancer growth and merits additional development. Citation Format: Takahito M. Miyake, Sunila Pradeep, Behrouz Zand, Heather J. Dalton, Yunfei Wen, Guillermo N. Armaitz Pena, Michael Kauffman, Dilara McCauley, Sharon Shacham, John E. Wiktorowicz, Anil K. Sood. Therapeutic targeting of CRM1 in ovarian cancer. [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 5541. doi:10.1158/1538-7445.AM2013-5541
Abstract 3082: A paradoxical suppressive role for Src in urothelial carcinoma
Authors: Courtney Pollard, Shibu Thomas, Michael A. Harding, Dan Theodorescu
Journal: Cancer Research (2010)

Abstract The most prevalent type of bladder cancer in western nations is urothelial carcinoma (UC). A significant number of patients with UC present with the muscle invasive form of the disease that is treated by radical cystectomy. Even with these treatments approximately 50% of these patients will develop metastases, resulting in essentially incurable disease. Thus, understanding the molecular basis of metastases in UC may prove useful in providing new therapeutic insights and targets. Src (v-Src sarcoma viral oncogene homolog) has been found to play pivotal oncogenic roles in a variety of in vitro and in vivo cancer models. Interestingly, when Src expression and activity was evaluated in a panel of bladder cancer cell lines and human bladder cancer tissue, it was shown that there was an inverse correlation between Src expression/activity and bladder tumor grade, suggesting that the Src oncogene might play a paradoxical suppressive role in UCs. Herein, we show that that stable expression of constitutively active Src in a high grade bladder cancer cell line (UMUC3) corresponds to a decrease in in vitro monolayer growth (p = 0.05), Boyden Chamber migration (over a period of time where growth effects are inconsequential) (p &amp;lt; 0.01) and a reduction of experimental lung metastases in nude mice (p &amp;lt; 0.036). Supportive of this surprising finding that Src is a suppressor of various malignant phenotypes, we demonstrate that pharmacological inhibition of Src tyrosine kinase activity in the KU7 non invasive UC cells that have high Src expression and tyrosine kinase activity increases cellular proliferation and anchorage independent growth, compared to carrier treated controls. Interestingly, we show that stimulation of FGFR3, a tyrosine kinase receptor that has been associated with low grade and stage non- invasive bladder cancers with favorable prognoses, leads to induction of Src kinase activity in the KU7 cell line. Taken together, these data suggest direct evidence that Src acts paradoxically as a suppressor or aggressive urothelial cancer phenotypes and provide a possible explanation how FGFR3 activity may maintain a non aggressive tumor phenotype. 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 3082.
Gene associations and risk of breast cancer.
Authors: RG Andavolu, LA Cone, S Shu, C Izsac, MV Andavolu, M Luthra
Journal: Cancer Research (2009)

Abstract Abstract #3094 Background: Human BCCIPalpha (Tok-1alpha) was identified as a BRCA2 and CDKN1A (p21, or p21(Waf1/Cip1)) Interacting Protein. BCCIP binds to a highly conserved domain proximate to the C-terminus of BRCA2 protein and the C-terminal domain of the CDK-inhibitor p21. Previous reports showed that BCCIP alpha enhances the inhibitory activity of p21 toward CDK2 and that BCCIP alpha inhibits the growth of certain tumor cells. In cancers harboring wild type p53, the p53 transactivation activity may be compromised by other mechanisms. It is clear from previous reports that BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 and BCCIPalpha is an important cofactor for BRCA2 in tumor suppression. In this study, specific SNPs in BCCIP, CDKN2A, BRCA2 and KLF6 (tumor suppressor gene) were screened to evaluate the potential influence of these genes in the predisposition to breast cancer.&amp;#x2028; Materials &amp; Methods: Blood was drawn from 204 primary breast cancer patients and 197 normal healthy subjects. An informed consent was obtained from all the study subjects. Genotyping was done using polymerase chain reaction followed by restriction enzyme digestion. SPSS version10.1 for windows software was used for data analysis.&amp;#x2028; Results: A relatively high frequency of the mutant alleles showing significant association with breast cancer was observed when compared with age, gender and ethnic matched control subjects (KLF6- p&amp;lt;0.0001; BRCA2- p&amp;lt;0.028; CDKN2A- p&amp;lt;0.018). Association among these gene variables were determined using spearman correlation coefficients. Significant correlations were observed among BCCIP-BRCA2 (p&amp;lt; 0.003); BCCIP-CDKN2A (p&amp;lt; 0.004), BRCA2-CDKN2A (p&amp;lt;0.037) genes.&amp;#x2028; Conclusions: Our results confirm the strong correlation of BCCIP gene with BRCA2 and CDKN2A gene. A strong association of KLF6 (tumor suppressor gene) gene with breast cancer was observed but no such correlation was identified with BCCIP, CDKN2A and/or BRCA2 suggesting that KLF6 gene may be involved in tumorigenesis using different regulating pathway. To better understand the role of these genes in the progression of breast carcinoma, gene expression studies will be performed using quantitative PCR. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3094.
Reticuloendothelial "Activation" Noted After Splenectomy for ITP and Presence of a Post-Poliomyelitis Asymmetry
Authors: RICHARD P. SPENCER, PARDEEP MITTAL
Journal: Clinical Nuclear Medicine (1998)

A radiocolloid study was carried out, after splenectomy, in a 75-year-old man who had idiopathic thrombocytopenic purpura. The patient, who did not have an increase in platelet counts after spleen removal or after platelet infusions, showed radiocolloid accumulation in the lungs and in the bone marrow. This suggested some"activation" of reticuloendothelial cells, perhaps by circulating immune complexes. The left femur (site of an episode of poliomyelitis many years previously) had less radiocolloid uptake than the right.
Placebo Effects in Medicine
Authors: Ted J. Kaptchuk, Franklin G. Miller
Journal: New England Journal of Medicine (2015)

Interview with Prof. Ted Kaptchuk on the outlook for harnessing the benefits of placebo effects in medicine. (12:51)Download Research has revealed placebo effects to be genuine biopsychosocial phenomena representing more than simply spontaneous remission or normal symptom fluctuations. How can this understanding be used to benefit patients?
Consolidation of regulation in Europe is needed for the ICMJE’s data sharing proposal to work
Authors: Marc Dewey, Jonathan Dodd
Journal: BMJ (2016)

The International Committee of Medical Journal Editors (ICMJE) proposes an important step towards better use of clinical trial data.1 Two pivotal aspects about this proposal, planned to become effective in 2017, require thought.

Firstly, even in large scale studies investigating common clinical conditions such …
Abstract ADV13: Kure It Cancer Research.
Authors: Karen Jones
Journal: Cancer Research (2013)

Abstract Kure It funds researchers conducting innovative projects in the fields of kidney cancer and other underfunded malignancies. Kure It raises funds inseveral ways: through annual special events; contributions from family and community foundations; and partnerships with the self storage industry, through which we've created tailored programs and events aimed at raising funding and awareness. Since its inception in 2007, Kure It has raised over $1.6 million for research. Our goal is to raise $1 million annually going forward. In 2012, Kure It awarded grants totaling $900,000, including two $250,000 awards given through Kure It's partnership with the AACR. Kure It funds support the work of researchers at major cancer centers across the United States. Citation Format: Karen Jones. Kure It Cancer Research. [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 ADV13. doi:10.1158/1538-7445.AM2013-ADV13
Bone Scintigraphy and CT Findings in Transverse Process Apophysitis
Authors: Sumeet G. Dua, Amjad Ali
Journal: Clinical Nuclear Medicine (2016)

A 14-year-old avid gymnast presented with recent onset of increasing lower thoracic back pain. Clinical examination revealed point tenderness at about T10 level. Focal uptake was seen to the left of the midline on a bone scan ordered to exclude stress fracture. Spine CT when read in conjunction with the bone scan revealed apophysitis of the transverse process. Apophysitis of the posterior elements of the vertebrae is a rare cause of back pain in adolescents.
SP0201 Usefulness and Limitations of DXA for Diagnosing Osteoporosis
Authors: J.E. Compston
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> The inverse relationship between areal bone mineral density (BMD), measured by dual energy X-ray absorptiometry (DXA), and fracture risk in postmenopausal women and older men is well documented and is widely used in clinical practice to predict fracture risk, to aid treatment decisions and to monitor therapy. The proximal femur and lumbar spine are the most commonly measured sites; however, particularly in older people, the accuracy of lumbar spine measurements may be impaired and the proximal femur is most commonly used in the prediction of fracture risk. In addition, lateral views of the spine obtained by DXA are used to detect vertebral fracture and single energy images of the proximal femur can be used to visualize features associated with the development of atypical femoral fracture. Although DXA-derived BMD has high specificity in predicting fracture risk its sensitivity is low, so that the majority of fragility fractures occur in individuals who do not have osteoporosis as defined by a BMD T-score ≥-2.5. BMD does not capture all aspects of bone microarchitecture, structure and quality that influence bone strength and fracture risk. In addition, the effect of risk factors such as previous fracture, parental history of hip fracture, glucocorticoid therapy, bone turnover and falls on fracture risk are partially independent of BMD. Algorithms such as FRAX that incorporate some of these factors are widely used and in the future, additional refinements may improve further our ability to predict fracture risk in clinical practice. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6150
AB0908 Spinal mobility measures are dependent on age – the mobility study:
Authors: S. Ramiro, C. Stolwijk, A. van Tubergen, D. van der Heijde, R. Landewé
Journal: Annals of the Rheumatic Diseases (2013)

Background Spinal mobility is one of the core outcomes recommended by the Assessment of Spondyloarthritis international Society (ASAS) in the follow-up of patients with axial spondyloarthritis (SpA). It is, however, currently unknown what are the reference values for the recommended spinal mobility measures in healthy subjects and to what extent they are influenced by age. Objectives To assess the effect of age on spinal mobility measures among healthy people. Methods A cross-sectional study (``MOBILITY study") was conducted among healthy volunteers aged 20-69 years old. Recruitment was stratified by gender, age (10-year categories) and height (10cm categories). Participants were anyone Caucasian volunteering to be measured in the Netherlands and Portugal. Exclusion criteria were factors potentially influencing spinal mobility (eg. back surgery, low back pain). Several spinal mobility measures (see table) were investigated and they were compared across all age categories with analysis of variance followed by analyses to identify which groups were significantly different. The population was further divided according to the cutoff of 50 years old. The mean values were compared by independent sample t-test, Mann Whitney and chi-square, as appropriate. The Bath Ankylosing Spondylitis Mobility Score (BASMI) was calculated, according to its original definition (with cervical rotation in lying position and 15cm Schober) and also as recommended by the ASAS (with cervical rotation in sitting position and 10cm Schober). Results A total of 393 volunteers were included, 51% males and with a mean age of 43.9 (SD 13.9) years. A significant decrease in all spinal mobility measures with increasing age was found, particularly between the older categories (50-59 and 60-69 years) and the younger categories (20-29 and 30-39). For instance, a cervical rotation of 79 (SD 9) was obtained for the 20-29 category, 78 (SD 10) for the 30-39 category, 75 (SD 10) for the 40-49 category, 71 (SD 8) for the 50-59 category and 66 (SD 10) for the 60-69 category, with a significant difference between each of the first three and the last two categories. Thereafter, the population was divided according to the cutoff of 50 years old, as axial SpA is rarely diagnosed after the age of 50, and a reference value for spinal mobility is therefore most relevant in this age category. There were significant differences in all the measures between the two age groups (table). View this table: Table 1. Comparison of spinal mobility measures between people younger and older than 50 years of age Conclusions All spinal mobility measures significantly decrease with increasing age, which should be taken into account when assessing older patients. Disclosure of Interest None Declared