tbuckley/cabot-search huggingface dataset:
Abstract 3125: Upregulation of gap junctions with substituted quinolines in colon cancer cells
Authors: Kristina M. Bigelow, Thu Annelise Nguyen
Journal: Cancer Research (2011)

Abstract Colon cancer is one of the most common cancers in the United States with a high predisposition to metastasize. Furthermore, 30-40% of patients have metastatic disease at the initial diagnosis. Cancer cells exhibit many deficiencies in cell-to-cell communication, particularly gap junctional intercellular communication (GJIC). GJIC has been reported to diminish as cancer cells progress. Gap junctions are intercellular channels composed of connexin proteins, which mediate the direct passage of small molecules from one cell to the next. They are involved in the regulation of cell cycle, cell differentiation, and cell signaling. Previous work demonstrated that connexin proteins such as Cx43, Cx32 and Cx26 have a distinct pattern in SW480, SW620, HT29 and Caco-2 human colon cancer cell lines. The findings suggest that the lack of GJIC, in part due to low level of connexin, may contribute to facilitate colon cancer progression. Since the regulation of gap junction is lost in colon cancer cells, the goal of this study is to restore GJIC in colon cancer cells. Recently, substituted quinolines (PQs), gap junction enhancers, have been shown to increase gap junction activity in breast cancer cells. The level of Cx43 is low in SW620 and SW480 human colon cancer cells. Transfected Cx43 cells have a 6-fold increase of gap junction activity compared to control using scrape load/dye transfer assay. Western blot analysis confirmed that a significant level of Cx43 was expressed in transfected Cx43 cells compared to control. This suggests that overexpressing Cx43 can restore GJIC. Interestingly, 200 nM PQ1 causes a 4-fold increase of gap junction activity as well and subsequently causes a decrease in cell proliferation by 15%. However, TPA, GJIC inhibitor, can reverse the gap junction activity of transfected Cx43 or treated PQ1 cells. Further analysis of Cx43, survivin, and cyclin D1 in treated cells was observed. Overall, the results show that substituted quinolines can directly enhance gap junction activity and attenuate cell proliferation in colon cancer cells. The findings provide an important implication in which restoration of gap junction activity can be targeted for drug development. 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 3125. doi:10.1158/1538-7445.AM2011-3125
P87 Vascular Adhesion Protein-1 promotes increases in liver infiltrating CD4+ T cells and NKT cells and induction of fibrogenesis in steatohepatitis
Authors: L. C. Claridge, C. J. Weston, E. L. Haughton, N. Westerlund, G. M. Reynolds, P. F. Lalor, J. W. Tomlinson, D. J. Smith, C. P. Day, D. H. Adams
Journal: Gut (2011)

<h3>Introduction</h3> Vascular Adhesion Protein-1 (VAP-1) is an adhesion molecule and membrane-bound amine oxidase. Our group has previously demonstrated that VAP-1 is able to support lymphocyte recruitment across human hepatic sinusoidal endothelium in vitro. Soluble VAP-1 (sVAP-1) is released into the circulation from adipose tissue and the hepatic vascular bed, has insulin like effects and is capable of inducing and propagating oxidative stress. <h3>Aim</h3> To investigate the role of VAP-1 in the progression of steatosis to steatohepatitis and cirrhosis. <h3>Method</h3> Human hepatic VAP-1 expression was determined using immunofluorescent labelling and multicolour confocal microscopy. Serum sVAP-1 levels were measured by ELISA in 144 patients with histologically graded NAFLD and 74 controls matched for age and metabolic phenotype. Two murine models of steatohepatitis were studied; (1) a methionine choline deficient diet was administered for 6 weeks in wild-type (WT) mice, WT mice treated with anti-VAP-1 antibody, and VAP-1 null mice (n=6 per group), 2) A western lifestyle model incorporating high trans-fat diet and fructose supplemented drinking water was administered to WT and VAP-1 null mice for 6, 9 and 12 months (n=10 per group). Control animals remained on normal chow. Liver infiltrating lymphocytes were identified and quantified using flow cytometry. Fibrosis was assessed by immunohistochemistry and qRT-PCR for aSMA and collagen I. <h3>Results</h3> (1) Human studies: We report increased hepatic expression of VAP-1 in NAFLD associated with elevated serum levels of sVAP-1 compared with controls (946±468 ng/ml vs 265±78 ng/ml, p&lt;0.0001). Multiple regression modelling reveals sVAP-1 to be the best predictor of histological fibrosis in our cohort. We detected strong VAP-1 expression in fibrotic septa co-localised with activated liver myofibroblasts (aLMF). In vitro human aLMF expressed and released sVAP-1 which promoted lymphocyte migration through a novel H<sub>2</sub>O<sub>2</sub>-mediated enzyme-dependent mechanism. (2) Experimental steatohepatitis: VAP-1 null and/or antibody treated mice developed fewer inflammatory foci and delayed onset of fibrosis in two murine models of NASH. In both models there was a specific failure to expand the intrahepatic CD4+ and NKT cell populations in VAP-1 null mice compared with 2 to 3-fold increases in WT mice. Three WT animals developed hepatocellular carcinoma by 12 months in the western lifestyle model but no tumours were found in VAP-1 null mice. <h3>Conclusion</h3> Our results implicate an important role for VAP-1 in steatohepatitis, in both humans and mice. The ability to target VAP-1 with antibodies or small molecule inhibitors makes it an attractive therapeutic target.
THU0035 Thrombin and plasmin induced proteoglycan release in human cartilage is par-dependent
Authors: L. Nieuwenhuizen, R. Schutgens, G. Roosendaal, S. Mastbergen, D. Biesma, F. Lafeber
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) and Rheumatoid Arthrisis (RA) are characterized by degradation of the cartilage. Proteases of the coagulation cascade and the fibrinolytic system, such as thrombin and plasmin, are elevated in both plasma and synovial fluid of OA and RA patients and are able to induce cartilage degradation. Cross-talking between coagulation and inflammation is mediated by protease-activated-receptors (PARs), which are expressed at increased level in OA and RA cartilage. These receptors are activated through cleavage by serine proteases, such as thrombin and plasmin. RNA interference is a process in which genes can be silenced sequence-specific. This can be invoked by transfection of tissue/cells with small interfering RNA (siRNA). <h3>Objectives</h3> Our aim was to study whether the thrombin- and plasmin-induced cartilage damage in human cartilage was PAR-dependent. <h3>Methods</h3> Full-thickness OA human articular cartilage tissue was obtained during total knee surgery. Slices of cartilage were cut aseptically from the articular surface. Within 1 hour of dissection the slices were cut into square pieces, weighed aseptically (range, 5.0 to 15.0 mg) and each sample was individually put into culture. Cartilage was cultured for 4 days in the presence of different concentrations thrombin (10, 30, or 100nM), or plasmin (10, 30, or 100nM). In addition, cartilage was transfected with PAR1-4 small interfering RNA (600nM) or control siRNA (600nM), and cultured with thrombin (100nM) or plasmin (100nM). Cartilage matrix turnover, in terms of proteoglycan release, was determined at day 4. To investigate the silencing effect of the siRNA transfection, RNA was extracted and PAR1-4 mRNA expression was analyzed with RT-PCR. <h3>Results</h3> Thrombin and plasmin increased proteoglycan release in human cartilage in a dose-dependent and statistically significant manner (500% for thrombin at 100nM; 217% for plasmin at 100nM). Thrombin- and plasmin-induced proteoglycan release was statistically significant reduced with PAR1-4 siRNA (60% for thrombin at 100nM; 54% for plasmin at 100nM). Control siRNA failed to reduce thrombin- and plasmin-induced proteoglycan release. Transfection with PAR1-4 siRNA resulted in complete suppression of PAR1-4 mRNA expression, whereas no effect of control siRNA on PAR1-4 mRNA expression was noted. <h3>Conclusions</h3> These results demonstrate for the first time that thrombin and plasmin-induced proteoglycan release in human cartilage is PAR-dependent and offer promise for the use of siRNA as a new strategy for therapeutic intervention in OA and RA. <h3>Disclosure of Interest</h3> L. Nieuwenhuizen Grant/Research support from: unrestricted grant from Novo Nordisk, R. Schutgens: None Declared, G. Roosendaal: None Declared, S. Mastbergen: None Declared, D. Biesma: None Declared, F. Lafeber: None Declared
The "Hug" View: An Image That Results in Optimal Visualization of the Upper Posterior Thorax
Authors: Loretha Freeman, Darlene Fink-Bennett
Journal: Clinical Nuclear Medicine (1999)

The bone scan is a sensitive indicator of osseous abnormalities. Its sensitivity depends on visualization of all bony structures. A portion of the thorax can be obscured by a scapular lesion or may appear as if one is present because of the superimposition of a portion of the scapula on a rib. To differentiate osseous abnormalities from superimposed Tc-99m MDP or to better view the posterior thorax, winged scapular views are best. If complete visualization is desired, the "hug" view should be used.
VASCULAR RESPONSE TO EVEROLIMUS AND BIOLIMUS-ELUTING CORONARY STENTS VERSUS EVEROLIMUS-ELUTING BIORESORBABLE SCAFFOLDS: AN OPTICAL COHERENCE TOMOGRAPHY SUBSTUDY OF THE EVERBIO II TRIAL
Authors: Zacharenia Kallinikou, Serban Puricel, Sonja Lehmann, Diego Arroyo, Mario Togni, Malica Cook, Gerard Baeriswyl, Jean-hristophe Stauffer, Jean-Jacques Goy, Stephane Cook
Journal: Journal of the American College of Cardiology (2015)
S127 Clinical Implementation Of Exercise Therapy During Critical Illness: A Longitudinal Observational Cohort Study
Authors: K. Roberts, B. Connolly, A. Curtis, C. Whiteley, N. Hart
Journal: Thorax (2014)

<h3>Introduction</h3> The practice of early exercise in the intensive care unit (ICU) is now receiving increasing clinical and research recognition. In order to determine the true effect of enhanced exercise therapy interventions, facilitate comparison across multiple datasets, and gain a better understanding of international practices, accurately defining ‘usual care’ is of vital importance.<sup>1</sup> The objective of this study was to benchmark current provision of exercise therapy within the ICU of a large, university teaching hospital, including ‘dose’ of exercise therapy provided, clinical factors influencing intervention delivery, and whether service provision met published national guidelines. <h3>Method</h3> A single-centre, prospective longitudinal observational study was conducted. Eligible patients were adults (≥18 years) receiving mechanical ventilation for at least 48 h, with no additional exclusion criteria. Consecutive eligible patient admissions were included. Data collection occurred remotely and independently, over a three month period, and using two electronic hospital databases to collect clinical, therapy and administrative data. <h3>Results</h3> One hundred and fourteen patients were included between February and April 2014 (median (IQR) age 61.5 (45.8–74.0)years, M:F 51:53, admission diagnosis 71% medical, mean (SD) APACHE II score 19.1 (4.8), ICU length of stay 16 (10–22)days). Complete data analysis is currently reported for 50 patients. Physiotherapy contact and milestone data are reported in Table 1. Nineteen patients did not receive exercise therapy during their admission. In those patients receiving exercise therapy, sitting over the edge of the bed was the highest level of physical activity achieved and the most frequently performed. Exercise therapy was most commonly delivered to those patients with either a tracheostomy or own airway, and once spontaneous modes of ventilation had been commenced. <h3>Conclusion</h3> These data represent initial analysis from a detailed description of exercise therapy delivered in a large, university hospital ICU. Completion of data analysis for the whole cohort is required to fully conclude what constitutes typical practice in this ICU, characteristics of patients receiving exercise therapy, and the influence of airways status on delivery of exercise therapy activities. <h3>Reference</h3> Parker A, Tehranchi K, Needham D. Critical care rehabilitation trials: the importance of ‘usual care’.<i> Critical Care</i> 2013;17(5):183
Peripheral Causes of Cognitive Motor Dissociation in Patients With Vegetative or Minimally Conscious State
Authors: Nicola Latronico
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Lymphovascular Invasion in BRCA Related Breast Cancer Compared to Sporadic Controls.
Authors: P. van der Groep, M. Heerma van Voss, J. Bart, E. van der Wall, P. van Diest
Journal: Cancer Research (2009)

Abstract Background: Germline mutations in the BRCA1 and BRCA2 genes predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumours serves several purposes. Biomarkers can contribute to the selection of high-risk patients for genetic screening, help to identify the pathogenicity of so called “unclassified variant” mutations, and insight in the carcinogenetic pathways allows to develop new targeted therapies. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels, and are often of the medullary (like) type that has a low rate of lymphovascular invasion (LVI), we hypothesized that absence of LVI could characterize BRCA1 related breast cancer.Methods: A population of 68 BRCA1 and 10 BRCA2 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumour type.Results: LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P=0.54, OR=1.29, CI 0.58-2.78). No significant differences were found for the BRCA2 group either (P=1).Conclusion: LVI seems to occur as much in BRCA1 germline mutation related breast cancers as in sporadic controls. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation, indicating that these cancers may have specific vasculoinvasive properties. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6019.
CHA2DS2-VASC SCORE AND ADVERSE EVENTS IN PATIENTS WITH HEART FAILURE AND SINUS RHYTHM
Authors: Siqin Ye, Min Qian, Bo Zhao, Gregory Lip, Richard Buchsbaum, Ralph Sacco, Bruce Levin, Marco Di Tullio, Douglas Mann, Patrick Pullicino, Ronald Freudenberger, John Teerlink, J.P. Mohr, Susan Graham, Arthur Labovitz, Conrado Estol, Dirk Lok, Piotr Ponikowski, Stefan Anker, John Thompson, Shunichi Homma
Journal: Journal of the American College of Cardiology (2016)
P15.07 * VISUOSPATIAL AND VISUO-CONSTRUCTIVE ABILITIES IMPAIRMENT AFTER RIGHT OCCIPITAL EXTRAXIAL LESION: CASE REPORT
Authors: C. Sindorio, R. V. Abbritti, C. Mento, M. C. Quattropani, A. Germano
Journal: Neuro-Oncology (2014)

INTRODUCTION: It is widely reported in literature that parietal and occipital lesions, especially when located on the right brain hemisphere, may be associated to visuospatial and visuo-constructive impairment. Psychiatric patients suffering from bipolar disorder and treated with lithium in association with brain tumors, present neuropsychological deficits in several domains such as memory, attention and executive functions. In the present study we describe the case of a 43 years old female, lawyer, with a child, and an adequate social and working background, affected by a right occipital extraxial lesion. Her clinical history was characterized by a previous diagnosis of bipolar disorder treated with lithium, and of breast cancer treated through a multidisciplinary protocol of surgery, chemotherapy and radiotherapy. In contrast to previous data, the preoperative cognitive assessment of the patient reveals only a mild visuospatial and visuo-constructive impairment in addition to an excellent performance in memory, attention, language and executive functions. The patient underwent to microsurgical removal of the lesion and the three days post-op later cognitive evaluation showed the complete resolution of pre-op visuospatial and visuo-constructive impairment. The experience of our institution, through the analysis of this case, focuses on higher education's level, younger age and adequate social and working environment as effective predictive factors of post- operative cognitive improvement. MATERIALS AND METHODS: We performed a pre and post-operative neuropsychological assessment through MMSE and RBANS, a brief, fast and simple neuropsychological battery which assesses 5 different domains: immediate memory, visuospatial and visuo-constructive abilities, attention, language comprehension and delayed memory, minimizing the effect of cognitive strain. RESULTS: We observed a preoperative mild visuospatial and visuo-constructive impairment with preserved immediate and delayed memory, language and attention and the complete resolution of visuospatial and visuo-constructive impairment after surgical treatment. DISCUSSIONS: The analysis of the key aspects of this case reinforces the association between higher education's level, younger age and better pre-op neuropsychological performance as predictive factors of post-op cognitive improvement in patients suffering from brain tumors and psychiatric disorders.
AB0355 Hearing Impairment Seems to BE Associated to A Higher Disease Activity in Rheumatoid Arthritis Patients. A CASE Control Study
Authors: R. Ilham, R. Hanan, E.A. Ali, D. Taoufik, E. Leila, H.H. Najia
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The aim of this study was to evaluate the pattern of hearing impairment in Rheumatoid Arthritis (RA) patients compared to healthy controls and to examine associations between hearing impairment and disease activity of RA assessed by the disease activity index-DAS 28. <h3>Methods</h3> This is a cross-sectional study with 2 groups: 22 RA patients (20 women and 2 men, mean age of 44.2 years, disease duration median of 41 months (21, 141)) and 17 healthy subjects (13 women and 4 men, mean age of 41 years) apparied for age and sex. No subject of the 2 groups has had any abnormalities at otoscopic examination. Hearing impairment was evaluated by pure tone audiometry and tympanometry including the static compliance, middle ear pressure, stapedial reflex threshold test. RA disease activity was assessed using the DAS28 (remission was defined by a DAS 28&lt;2.6). <h3>Results</h3> Conductive hearing loss (CHL) was found in 14 patients vs 2 controls (p=0.05). The stapedial reflex was absent in 10 RA patients vs none in healthy controls (p=0.04). Sensorineural hearing loss (SNHL) was found in 4 patients and none in controls. Mixed hearing loss was found in 4 patients but none in controls. Hearing loss in RA was more prevalent in RA patients with an active disease (p=0.04) <h3>Conclusions</h3> This study suggests that hearing loss risk is higher in RA patients compared to healthy controls and seems to be associated to disease activity. Audiological evaluation should be performed periodically to identify possible audiological damage. Nevertheless, those results should also be confirmed by larger studies. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4609
Promises from Trametinib in RAF Active Tumors
Authors: Edward A. Sausville
Journal: New England Journal of Medicine (2012)

Progression of human cancer occurs through genetic changes in cancer cells that activate biochemical pathways governing hallmarks of cancer, including proliferation and tumor-cell survival,1 among others. Tumor growth factor receptors activate RAS oncoproteins, which subsequently activate a kinase cascade that includes RAF, MEK, and ERK kinases. This pathway is mutated to promote tumor growth in at least 20% of cancers.2 The RAS–MEK–ERK pathway is thus a focus of intense interest for the development of cancer drugs. First fruits from this quest have yielded drugs directed against growth factor receptors, including the monoclonal antibody trastuzumab and the small molecules erlotinib and . . .
Long-Term Mortality after Transfusion-Associated Non-A, Non-B Hepatitis
Authors: Leonard B. Seeff, Zelma Buskell-Bales, Elizabeth C. Wright, Stephen J. Durako, Harvey J. Alter, Frank L. Iber, F. Blaine Hollinger, Gary Gitnick, Robert G. Knodell, Robert P. Perrillo, Cladd E. Stevens, Charles G. Hollingsworth
Journal: New England Journal of Medicine (1992)

Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known.
Staphylococcal Psoas Abscess
Authors: R D Huhn, H P Dave
Journal: New England Journal of Medicine (1998)

Figure 1. A 42-year-old man with the acquired immunodeficiency syndrome was evaluated for cachexia, hepatosplenomegaly, and persistent fever that was unresponsive to therapy with a third-generation cephalosporin and vancomycin. He had no lumbosacral, perineal, or leg pain and no difficulty walking. He had not had any recent infections of the skin or other sites. His white-cell count was 5700 per cubic millimeter (79 percent neutrophils). Computed tomography (CT) of the abdomen after intravenous administration of radiographic contrast material revealed bilaterally enlarged psoas muscles (long arrows in Panel A) with hypodense centers and thin residual rims of normally attenuating tissue; the . . .