tbuckley/cabot-search huggingface dataset:
Abstract 740: Investigating the role of epigenetic mechanisms upon aberrant signaling network activation.
Authors: Behnam Nabet, Rosemary Braun, Relja Popovic, Jonathan D. Licht
Journal: Cancer Research (2013)

Abstract Growth factor (GF) stimulation of quiescent cells activates critical receptor tyrosine kinase (RTK) signaling pathways as well as waves of downstream gene expression to drive cell proliferation, survival, and migration. Aberrant activation of RTK signaling networks is a root cause of the uncontrolled cell growth and cell survival seen in cancer. In this study, we aim to uncover the role of epigenetic mechanisms in controlling the dynamic gene expression changes that occur as a cell is activated from a quiescent state, in normal and oncogenic cellular contexts. In order to compare controlled RTK signaling with hyperactive RTK signaling cellular states, we created a cell culture system to modulate the duration and intensity of RTK activation. We genetically deleted the Sprouty (Spry) genes, a family of negative feedback inhibitors of RTK signaling that function as putative tumor suppressors. The Spry deficient cells are hypersensitive to several GFs and show significantly enhanced and prolonged activation of several critical RTK signaling pathways, including the Ras-MAPK pathway. Additionally, the Spry deficient cells possess accelerated cell growth and increased tumorigenic potential compared to their wild-type counterparts. To determine whether this deregulated signaling results in aberrant gene expression, quiescent Spry wild-type and deficient cells were stimulated with GFs, and microarrays were used to profile changes in gene expression over time. Deregulated RTK signaling due to the absence of Spry leads to abnormal expression of a large subset of genes. Specifically, many genes display display not only changes in the level of expression, but aberrant patterns of response to GF stimulation. We determined that genes with deregulated activation in Spry deficient cells display significant differences in histone tail modifications at promoter regions and distal regulatory elements. Interestingly, these changes are evident in the quiescent cellular state as well as upon GF-mediated RTK network activation. Our work suggests that dynamic changes in a cell's epigenetic landscape contribute to the deregulated activation of genes upon hyperactive RTK signaling. Our study will provide a comprehensive view of how epigenetic mechanisms contribute to aberrant gene expression in oncogenic cellular contexts. Citation Format: Behnam Nabet, Rosemary Braun, Relja Popovic, Jonathan D. Licht. Investigating the role of epigenetic mechanisms upon aberrant signaling network activation. [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 740. doi:10.1158/1538-7445.AM2013-740
Depression and physician assisted dying
Authors: M. L v. d. Lee
Journal: BMJ (2008)

Preventing depression, not physician assisted suicide, is the priority 

In the linked study (doi:10.1136/bmj.a1682), Ganzini and colleagues report that most terminally ill patients in Oregon who receive physician assistance in dying do not have depressive disorders.1 In fact, only three (17%) patients who received a lethal prescription met criteria for depression. This finding is in line with a previous study carried out in the Netherlands, where both euthanasia and physician assisted suicide are legal. A major depressive disorder was identified in only two terminally ill oncology patients (17%) at the time they explicitly requested euthanasia.2 This suggests that the prevalence of major depression among patients requesting euthanasia or physician assisted dying is much lower than would be expected from studies on the relation between depression and the desire to die in areas where assisted dying is illegal.

Despite this outcome, depressed mood and an explicit request for euthanasia were associated in terminally ill patients with cancer …
Abstract 899: TMPRSS2:ERG urine test identifies Gleason score upgrading and significant prostate cancer
Authors: Sheila M. Aubin, Scott Tomlins, Sarah Meyer, Yvonne Penabella, Javed Siddiqui, John Wei, Arul Chinnaiyan, Harry Rittenhouse, Jack Groskopf
Journal: Cancer Research (2011)

Abstract Objective: In men diagnosed with prostate cancer (PCa) at biopsy, a major challenge is correctly stratifying those with indolent versus significant PCa for treatment selection. The extent and grade of PCa is assessed in part based on standard risk factors, biopsy Gleason score (bx GS) and the number of positive biopsy cores. However, due to under-sampling at biopsy, upgrading in Gleason score is often seen from biopsy to prostatectomy. In this study we evaluated a TMPRSS2:ERG (T2:ERG) urine test for its ability to identify significant cancer and upgrading at prostatectomy. Methods: Post-DRE urine specimens were prospectively collected from 218 men referred for prostatectomy. T2:ERG mRNA copies were quantified using a transcription-mediated amplification assay and normalized to PSA mRNA copies to calculate a T2:ERG score. The prototype T2:ERG urine assay detects the gene fusion mRNA isoform TMPRSS2 exon 1 to ERG exon 4. T2:ERG score was correlated to prostatectomy Gleason score (px GS) and significant cancer as defined by the Epstein criteria at prostatectomy. Results: Of 185 men scheduled for radical prostatectomy, 61 had low risk of significant cancer based on having bx GS&amp;lt;6 and % positive biopsy cores&amp;lt;33%, yet upon prostatectomy, 57% of these men were found to harbor a significant PCa. The T2:ERG assay identified an additional 31% prostatectomy significant cancer in the biopsy low-risk disease cancer group. In a multivariate model, adding T2:ERG to bx GS and % positive cores significantly increased the accuracy for predicting significant PCa at prostatectomy from 0.84 to 0.89 (p=0.0002). Sensitivity increased by 8% for detecting prostatectomy significant cancer when T2:ERG was added to these biopsy criteria (sens/spec=85%/87% vs 77%/87%). T2:ERG also significantly correlated with Gleason score upgrading from biopsy to prostatectomy (bx GS/px GS = 6/ 6 vs bx GS/px GS = 6/&amp;gt;7, p = 0.0076). At biopsy, 70 men were found to have low-grade cancer (bx GS&amp;lt;6), but upon prostatectomy, upgrading was seen in 50% of these men. T2:ERG was able to identify 40% of men with bx GS&amp;lt;6 that were later upgraded. Conclusions: A T2:ERG urine test may help identify significant cancers and Gleason score upgrading, and increase predictive accuracy when used in combination with currently available methods. 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 899. doi:10.1158/1538-7445.AM2011-899
Home Treatment of Tuberculosis
Authors: C. V. Ramakrishnan, S. Devadatta
Journal: BMJ (1966)

BEIAL JOURAL 1539scoliosis by a group, including an orthopaedic surgeon, an anatomist, a neurologist, a path- ologist, a radiologist, and perhaps an engineer with knowledge of the properties of materials and of stresses and strains.When the distorting forces causing scoliosis are further understood it will be much easier to determine their origin.The beginnings of such a study have already been started at the Brompton Hospital, and will soon be extended.I would welcome hearing from anyone interested in these wider aspects of this problem.-I am, etc.,
How Exposures to Biologics Influence the Induction and Incidence of Asthma
Authors: Darryl C. Zeldin, Peyton Eggleston, Martin Chapman, Giovanni Piedimonte, Harard Renz, David Peden
Journal: Environmental Health Perspectives (2005)

A number of environmental factors can affect the development and severity of allergy and asthma; however, it can be argued that the most significant inhaled agents that modulate the development of these conditions are biologics. Sensitization to environmental allergens is an important risk factor for the development of asthma. Innate immune responses are often mediated by receptors on mononuclear cells whose primary ligands arise from microorganisms. Many pathogens, especially viruses, target epithelial cells and affect the host immune response to those pathogens. The acquired immune response to an allergen is influenced by the nature of the innate immune system. Products of innate immune responses to microbes promote TH1-acquired responses. In the absence of TH1 responses, TH2 responses can dominate. Central to TH1/TH2 balance is the composition of contaminants that derive from microbes. In this review we examine the biology of the response to allergens, viruses, and bacterial products in the context of the development of allergy and asthma.
Calcium and magnesium sensitivity of the carotid baroreceptor reflex in cats.
Authors: D L Kunze
Journal: Circulation Research (1979)

The systemic blood pressure response to changes in carotid sinus pressure has been examined during variations in the calcium and magnesium concentration of the perfusate of the isolated sinus. The threshold for the blood pressure response was increased by 16 +/- 0.8% when calcium was raised from 1.1 mM (control) to 2.2 mM and increased by 27 +/- 1.8% when calcium was raised to 3.3 mM. The threshold was reduced by 21 +/- 0.7% in zero calcium and 13 +/- 0.8% in 0.55 mM Ca2+. The sensitivity (slope of the linear portion of the pressure response curve) of the reflex was not significantly changed except at 3.3 mM Ca2+ where it was reduced by 16 +/- 2.9%. Magnesium had directionally similar effects of a lesser magnitude. Earlier work described the reduced sensitivity and threshold of the baroreceptor reflex when sodium concentration in the carotid perfusate was reduced. The present study shows that reducing calcium attenuates the effect of lowered sodium and increasing calcium augments it. These results are discussed in terms of possible ionic influences on the receptor potential and spike generation.
A9.10 Neutralisation of ACPA – A Way to Go?
Authors: C. Cerqueira, E. Ossipova, M. Hansson, L. Mathsson, L. Klareskog, Johan Rönnelid, P-J Jakobsson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> In a previous study, we have identified endogeneously citrullinated sites in fibrinogen from RA synovial tissue (Hermansson, <i>et al</i>, 2010 in <i>Proteomics-Clin Appl</i>). Within the alpha chain, Arg573 and Arg591 were found citrullinated with an occupancy rate in the range of 1–2% and in the β-chain, Arg72 and Arg74 were also found citrullinated. We now demonstrate that these citrullinated residues are autoantigenic as well as demonstrate that peptides containing these epitopes can be used as probes for development of ACPA neutralising compounds. <h3>Materials and Methods</h3> The autoantigenic potential was investigated using the Phadia’s ImmunoCAP ISAC® system. Citrullinated and unmodified fibrinogen peptides were immobilised onto a glass slide in an arrayed fashion and serum from 404 CCP positive and 532 CCP negative RA patients and 461 healthy controls from the EIRA cohort were tested. We also assayed the identified citrulline fibrinogen peptides for their ability to prevent purified ACPA (Ossipova, <i>et al</i>, 2012 submitted) to bind to CCP (CCPlus® ELISA, Euro-Diagnostica AB). Peptides were individually or in combinations incubated with different ACPA pools and the blocking efficiency was expressed as percent of inhibition and IC50. Corresponding arginine peptides were used as controls. <h3>Results</h3> We found that 31% (87% are CCP positive) of patients were positive to Cit573 peptide. For the Cit591 peptide, the corresponding numbers were 10% (65%), for the Cit74 peptide 28% (68%) and for the Cit72 peptide 20% (68%). Interestingly, citrullinated 573 and Cit591 peptides revealed a maximum of 77% and 48% ACPA inhibition, respectively. When equally mixed, these peptides displayed an additive higher degree of ACPA neutralisation (84%). In contrast, Cit74 and Cit72 peptides reached a more modest maximum inhibition of 26% and 30%, respectively. This experiment was repeated using a different set of ACPA pool and then the efficiencies were lower for Cit573 (47%) but similar for Cit591 (51%). Logically, the efficiency of specific citrullinated compounds will depend on the individual ACPA specificities. <h3>Conclusions</h3> Here we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes found in RA synovial membranes. These peptides can now be used as additional biomarkers for studies of ACPA sub-specificity profiles as recently reported (Brink, <i>et al</i>, 2012 <i>A&amp;R</i>, in press). We also demonstrate that these citrullinated peptides can be used as neutralising agents blocking a significant portion of ACPA binding to CCP. These results open novel possibilities for the design of personalised ACPA blockers preventing for instance the osteoclastogenesis and bone loss induced by ACPA (Harre, <i>et al</i>, 2012 <i>JCI</i>).
Government sets up inquiry into ventilation trial
Authors: J. Jones
Journal: BMJ (1999)

An inquiry has begun into research conducted at the North Staffordshire Hospital after parents alleged that they were misled into consenting to experimental treatment for their premature babies.

A new type of ventilator was tested between 1989and 1993on 122babies who had breathing difficulties in a randomised controlled trial of a technique called continuous negative extrathoracic pressure (Pediatrics 1996;98:1154-60). Of these infants, 28died and 15sustained brain damage. In the control group, in which conventional treatment was given to the same total number of babies, 22died and 10sustained brain damage. The authors of the study and the hospital have claimed …
Comments on minimizing misdiagnosis of hepatocellular carcinoma from magnetic resonance imaging
Authors: Yun Ku Cho
Journal: Hepatology (2009)

I read with interest the article by Rimola et al.1 on the magnetic resonance (MR) findings of intrahepatic cholangiocarcinoma (ICC). The authors stated that the most characteristic MR contrast pattern for ICC in cirrhosis was progressive contrast uptake throughout the different phases, while contrast washout during delayed phases was not observed. As the authors pointed out, a significant number of ICC nodules were reported to display washout on dynamic computed tomography (CT) imaging, and this could be taken as a potential for a false positive diagnosis of hepatocellular carcinoma (HCC) if noninvasive diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD) guidelines are applied.1-3 This article suggests that a false diagnosis of HCC can be minimized based on the MR findings, especially for delayed imaging. I agree with the authors on the main concepts of the study, but I would like to make some comments as follows. First, the number of ICCs was relatively small, as the authors have pointed out in the text. Moreover, the diagnostic challenge between ICCs and HCCs is usually confined to small tumors less than 3 cm in size.2 The number of small ICCs less than 3 cm in size was only 20 in this series, and was not sufficiently large to allow for a decisive conclusion regarding a diagnosis. Second, the peripheral region of the medullary subtype of cholangiocarcinoma with abundant tumor cells is known to show prominent early enhancement on MR imaging.4 In fact, a small number of ICC tumors with early enhancement and delayed washout pattern on MR imaging have already been reported, although these are very rare.4, 5 Areas of an ICC with early enhancement and rapid washout pattern seem to indicate active growth.3 Again, I feel that a final conclusion for the specificity of delayed MR imaging requires further large-scale studies in patients with cirrhosis. In addition, some metastatic lesions from a hypervascular primary neoplasm can also show early enhancement and delayed washout of contrast material.6 However, in these tumors, washout is usually limited to the peripheral portion of the tumors (rim sign), which is a specific finding for the presence of a metastasis.6 Therefore, these observations would not weaken the strength of the present AASLD guidelines. It seems evident that the use of liver MR imaging, especially with delayed phase images, is very promising for the differential diagnosis of liver tumors. However, I think that the chance of a false diagnosis of an HCC can be minimized only when these potential limitations are considered together. Future large-scale studies will be essential to obtain definite diagnostic conclusions. Yun Ku Cho M.D.*, * Department of Radiology, Seoul Veterans Hospital, Seoul, Korea.
IMPORTANCE OF WESTERN BLOT ANALYSIS IN PREDICTING INFECTIVITY OF ANTI-HTLV-III/LAV POSITIVE BLOOD
Authors: JuanI. Esteban, Chang-Chih Tai, JohnW.D. Kay, J.Wai-Kuo Shih, AnneJ. Bodner, HarveyJ. Alter
Journal: The Lancet (1985)
Congenital Absence of the Ductus Deferens
Authors: Carl K. Pearlman
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In your QUESTIONS AND ANSWERS column (<b>213</b>:307, 1970) a consultant stated that congenital absence of the ductus deferens was not likely with ipsilateral normal testis. Several years ago, I attempted to perform a bilateral vas deferens ligation on a patient who had been explored elsewhere and found to have congenital absence of the kidney on the left side. I was unable to find a vas deferens on the left side and the epididymis itself was rudimentary. The testis itself grossly appeared to be normal in size, shape, and consistency. I am sure that this is a very rare condition but it can and does occur.
Dyskeratosis congenita: delay in diagnosis and successful treatment of pancytopenia by bone marrow transplantation
Authors: R.J. PHILLIPS, MARY JUDGE, D. WEBB, J.I. HARPER
Journal: British Journal of Dermatology (1992)

Journal Article Dyskeratosis congenita: delay in diagnosis and successful treatment of pancytopenia by bone marrow transplantation Get access R.J. PHILLIPS, R.J. PHILLIPS Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar MARY JUDGE, MARY JUDGE Departments of Dermatology Search for other works by this author on: Oxford Academic Google Scholar D. WEBB, D. WEBB Haematology, Hospitals for Sick Children, Great Ormond Street, London WCIN 3JH, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.I. HARPER J.I. HARPER Departments of Dermatology Dr J. Harper, Department of Dermatology, Hospitals for Sick Children. Great Ormond Street, London WCIN 3JH, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 3, 1 September 1992, Pages 278–280, https://doi.org/10.1111/j.1365-2133.1992.tb00128.x Published: 01 September 1992
P303 Does Regular Surveillance Ensure The Opportunity Of Non-invasive Ventilation To Patients With Motor Neurone Disease?
Authors: F. Thaivalappil, B. Kathiresan, M. Davies, I. Smith
Journal: Thorax (2014)

<h3>Introduction</h3> Most people with motor neurone disease (MND) die from respiratory failure and non-invasive ventilation (NIV) can improve survival. The median survival of patients with good bulbar function not treated with NIV was just 11 days in one RCT (1). We wished to establish whether our 3 monthly follow up regime, following NICE guidance (2), ensures all patients are offered NIV or whether many are dying without this treatment opportunity. <h3>Aim</h3> Establish what proportion of patients died before NIV was offered while under our follow up. <h3>Method</h3> A retrospective analysis of case notes of patients who died during the calendar year 2013. Survival was calculated as days (d) from starting of NIV until death. <h3>Results</h3> From our cohort, 24 patients died in 2013 of whom 20 had been offered NIV (17 compliant). Median survival was 390 (IQR 147–798) d. Median survival for NIV compliant patients was 462 (IQR 223–848) d. Median survival was 190 d for the 2 NIV compliant patients with severe bulbar dysfunction and 85 days for 3 patients who were non-compliant with NIV. Of the 4 patients who died before NIV was offered, 2 had severe bulbar dysfunction and 1 patient was on CPAP for treatment of obstructive sleep apnoea. Pneumonia was reported as the cause of death in 2 of these patients. Details of the mode of dying of the other 2 patients could not be established (certified as MND). <h3>Conclusion</h3> Most of the patients dying with MND had been offered NIV, 85% were compliant with treatment and survival was at least as good as published results. 4 died before NIV was offered but in 2, death was precipitant due to pneumonia, not ventilatory failure. As a default, 3 monthly review seems a reasonably safe interval for ventilatory surveillance in people with MND balancing intrusive hospital visits with the risk of missing the opportunity to try NIV at the end of life. <h3>References</h3> Bourke SC, <i>et al</i>. <i>Lancet neurol</i>. 2006; 5: 140-7 NICE guidelines (CG105). 2010. Use of NIV in the management of MND
Risk Factors for a Positive Tuberculin Skin Test among Employees of an Urban, Midwestern Teaching Hospital
Authors: Thomas C. Bailey
Journal: Annals of Internal Medicine (1995)

Objective: To determine the prevalence and incidence of and the relative risks for positive tuberculin skin tests among employees of a large, urban teaching hospital. Design: Retrospective cohort study. Setting: Barnes Hospital, St. Louis, Missouri. Participants: Hospital personnel employed at any time between January 1989 and July 1991. Results: 684 of 6070 employees screened (11.3% [95% CI, 10.4% to 12.1%]) had positive tuberculin skin tests. Factors associated with a positive result were age (odds ratio, 2.02 per decade [CI, 1.87 to 2.18]; P < 0.0001); black race (odds ratio, 1.58 [CI, 1.26 to 2.00]; P < 0.0001); Asian race (odds ratio, 16.7 [CI, 9.33 to 29.9]; P <0.0001); Hispanic ethnicity (odds ratio, 9.45 [CI, 3.58 to 25.0]; P <0.0001); and percentage of low-income persons within the employee's residential postal zone (odds ratio, 1.14 per 10% [CI, 1.05 to 1.23]; P = 0.001). Twenty-nine of 3106 employees who had at least two tests had skin-test conversions (0.93% [CI, 0.60% to 1.3%]); 15 of these conversions (52%) occurred among employees who had no direct contact with patients. Only the percentage of low-income persons within the employee's residential postal zone (odds ratio 1.39 [CI, 1.09 to 1.78]; P = 0.0075) was independently associated with conversion. Conclusions: The most important associations with a positive tuberculin skin test were older age, minority group status, and the proportion of low-income persons within the employee's residential postal zone. Skin-test conversion was independently associated only with the percentage of low-income persons in the employee's postal zone. Stratifying employees according to degree of contact with patients or according to departmental group was not useful in determining risk for a positive tuberculin skin test or for skin-test conversion. For certain groups of employees, an exposure to tuberculosis in the community probably poses a greater risk than exposure in the hospital setting.