tbuckley/cabot-search huggingface dataset:
Abstract LB-211: beta1 integrin targeting results in radiosensitization by controlling DNA repair mechanisms and chromatin organization
Authors: Ellen Dickreuter, Katja Storch, Iris Eke, Mechthild Krause, Michael Baumann, Nils Cordes
Journal: Cancer Research (2012)

Abstract Integrin-mediated cell-extracellular matrix (ECM) interactions confer cancer cell resistance to therapy. Our own data and data of others generated in three-dimensional (3D) ECM-based cell cultures and in vivo provided evidence that particularly beta1 integrin targeting potently reduces this resistance involving downstream integrin signaling mediators like focal adhesion kinase, cortactin and JNK1. However, it remains unknown whether beta1 integrin inhibition affects the repair of radiation-induced DNA double strand breaks (DSB) and their distribution in eu- and heterochromatic DNA regions. Here, we show that 3D growth (cell culture, xenograft models) increased the amount of heterochromatin in human head and neck squamous cell (HNSCC) and lung carcinoma cell lines relative to 2D, induced higher radioresistance, reduced the number of chromosomal aberrations and gammaH2AX/53BP1-positive foci, which was accompanied by a shift of the euchromatin-to-heterochromatin DSB distribution from a 2:1 (2D) to a 1:1 (3D). Upon beta1 integrin inhibition using the inhibitory monoclonal antibody AIIB2 or siRNA, cells grown in 3D or as xenografts in nude mice were radiosensitized or showed a significant growth delay, respectively. The disruption of beta1 integrin-mediated cell-ECM interactions induced an increase in heterochromatin levels indicated by HP1alpha and H3K9me3 elevation. In line with these findings was a strong impairment of both ATM and DNA-PK and their associated downstream signaling pathways (e.g. Chk2, Mre11, Nbs1, Rad50) in beta1 integrin inhibited, irradiated cells relative to IgG isotype controls. In contrast to unchanged number of heterochromatic foci identified in stably transfected HP1alpha cells, kinetic DSB measurements revealed an increased number of euchromatic foci upon beta1 integrin blocking, which evidently showed strongly perturbed DSB repair. In conclusion, our data generated in 3D cell culture and tumor xenograft models suggest a regulatory function of beta1 integrin signaling in the repair of radiogenic DSBs and the organization of chromatin. In addition to our understanding of the initial steps deactivated upon beta1 integrin blocking, these findings bridge membrane bound integrin function to nuclear DNA repair processes, thus providing further insights into how integrins confer cancer cell radioresistance and why integrin targeting is potentially useful as adjuvant to conventional radio- and radiochemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-211. doi:1538-7445.AM2012-LB-211
Improved Therapeutic Index by Leucovorin of Edatrexate, Cyclophosphamide, and Cisplatin Regimen for Non-Small-Cell Lung Cancer
Authors: J. S. Lee, H. I. Libshitz, F. V. Fossella, W. K. Murphy, A. C. Pang, S. M. Lippman, D. M. Shin, I. W. Dimery, B. S. Glisson, W. K. Hong
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Improved Therapeutic Index by Leucovorin of Edatrexate, Cyclophosphamide, and Cisplatin Regimen for Non–Small-Cell Lung Cancer Get access Jin S. Lee, Jin S. Lee * Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex * Correspondence to: Jin S. Lee, M. D., Department of Medical Oncology, Box 80, UT M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Herman I. Libshitz, Herman I. Libshitz Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank V. Fossella, Frank V. Fossella Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar William K. Murphy, William K. Murphy Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Arlita C. Pang, Arlita C. Pang Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Scott M. Lippman, Scott M. Lippman Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Dong M. Shin, Dong M. Shin Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Isaiah W. Dimery, Isaiah W. Dimery Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Bonnie S. Glisson, Bonnie S. Glisson Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Waun K. Hong Waun K. Hong Department of Medical Oncology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 13, 1 July 1992, Pages 1039–1040, https://doi.org/10.1093/jnci/84.13.1039 Published: 01 July 1992 Article history Received: 04 February 1992 Revision received: 21 April 1992 Accepted: 23 April 1992 Published: 01 July 1992
Airways Function During Mild Viral Respiratory Illnesses
Authors: W. WALLACE FRIDY
Journal: Annals of Internal Medicine (1974)

The effect of viral respiratory illnesses on pulmonary function was studied prospectively. Base-line studies on 52 normal subjects included a serum specimen, spirometry, lung volumes, "closing volumes," and maximal expiratory flow volume curves with air and with 80% helium and 20% oxygen (He-O2). Twenty-two subjects, 9 cigarette smokers and 13 nonsmokers, returned for serial studies at the onset of acute illness and at weekly intervals thereafter until after symptoms completely subsided. The illnesses were mild and similar except for greater duration of symptoms in smokers. Rhinovirus was the causative agent in 7 of 9 smokers and 9 of 13 nonsmokers. During illness pulmonary function changes occurred only in smokers and consisted of an increase in "closing volume" and a decrease in maximal expiratory flow rates with He-O2 at lung volumes near residual volume. The functional changes were reversible and are thought to indicate development or worsening of peripheral airways obstruction.
Pathological finger fracture
Authors: T. Rider, I. Baig, C. Sayer, A. Crown
Journal: BMJ (2013)

A 75 year old white woman presented to our hospital with pain in her left hand after hearing a crack when pushing herself up from sitting. She immediately felt pain in her little finger and was unable to use her hand.

Over the preceding two years she had become increasingly tired and weak. This had necessitated a stair lift to be installed into her home and she had become unable to lift a plate down from her kitchen shelves. She had developed bone pain in her spine, knees, ankles, and shoulders. She also reported polyuria but no polydipsia. In the five months before admission she had lost two stone (12.6 kg) in weight.

Clinical examination showed no lymphadenopathy, goitre, breast lumps, or organomegaly.

Initial blood tests showed urea of 13 mmol/L (reference range 1.7-8.3; 1 mmol/L=2.8 mg/dL), creatinine 101 µmol/L (44-80; 1 µmol/L=0.01 mg/dL), corrected calcium concentration 3.19 mmol/L (2.15-2.61; 1 mmol/L=4 mg/dL), phosphate 0.79 mmol/L (0.81-1.45; 1 mmol/L=3.1 mg/dL), albumin 41 g/L (37-49), adjusted magnesium 0.54 mmol/L (0.66-0.99; 1 mmol/L=2 mEq/L), total bilirubin 7 µmol/L (0-21; 1 µmol/L=0.06 mg/dL), alkaline phosphatase 931 IU/L (<55; 1 IU/L=0.02 µkat/L), alanine aminotransferase 8 IU/L (0-33; 1 IU/L=0.02 µkat/L), haemoglobin 118 g/L (115-165), and erythrocyte sedimentation rate of 14 mm in the first hour (0-15). What does the radiograph of her hand (fig 1⇓) show?





### 1 What does the radiograph show?

#### Short answer

The radiograph shows well defined osteolytic lesions in the fourth metacarpal. The other obvious area of abnormality is the proximal phalanx of the fifth finger, where changes in trabecular pattern, cyst formation, and cortical erosions can be seen. …
Bid to cut waiting lists has pushed safety down NHS agenda
Authors: Lisa Hitchen
Journal: BMJ (2006)

The government's focus on targets means that few NHS hospital trusts prioritise safety issues, one chief executive of a trust claimed last week.

As a result very few senior staff of trusts attend conferences like the one organised by the National Patient Safety Agency in Birmingham last week, said Stephen Ramsden, chief executive for Luton and Dunstable NHS Trust. Mr Ramsden was one of only five chief executives there.

During questions to Jane Kennedy, the health minister whose responsibilities include patient safety, Mr Ramsden said: “I'm not a big fan of the target culture. If half the attention had been given to patient safety as has been given to waiting times then more chief executives would be here and more would have been done.”

His remarks were greeted with widespread applause from …
Points from Letters: False Positive Tests for Abnormal Haemoglobins
Authors: J. S. Lilleyman
Journal: BMJ (1971)

glucose was measured sequentially, blood glucose remained below 20 mg/100 ml for longer than 24 hours.Furthermore, a hypo- glycaemic baby may develop symptoms after many hours of being asymptomatic.This occurred in an infant, seen some years ago, who had a blood glucose level of 15 mg/100 ml at 10 hours of age.He was asymptomatic and was not treated.The glucose level re- mained low until, at 75 hours of age, he had a convulsion which responded to intravenous
Effect of subcutaneous sumatriptan, a selective 5HT1 agonist, on the systemic, pulmonary, and coronary circulation.
Authors: P D MacIntyre, B Bhargava, K J Hogg, J D Gemmill, W S Hillis
Journal: Circulation (1993)

BACKGROUND Sumatriptan (GR43175) is a selective 5-hydroxytryptamine (5HT1) receptor agonist effective in the acute treatment of migraine. Recent in vitro experiments suggest that it has vasoactive properties in vascular beds distinct from the cerebral circulation. The object of this study was to assess the vasoactive effects of the standard 6-mg subcutaneous dose of sumatriptan used in migraine on the systemic and pulmonary circulations and the coronary artery vasculature. METHODS AND RESULTS Ten patients undergoing diagnostic coronary arteriography were studied with digital subtraction angiography and invasive hemodynamic monitoring. After subcutaneous injection of sumatriptan, there was no significant change in heart rate or ECG morphology. There was a significant rise in the systemic (20%, p &lt; 0.05 by ANOVA) and pulmonary artery (40%, p &lt; 0.05 by ANOVA) pressures. There was no change in cardiac output, but there was a significant increase in total systemic (27%, p &lt; 0.05) and total pulmonary vascular resistance (40%, p &lt; 0.05). Sumatriptan caused a significant reduction (p &lt; 0.001 by ANOVA) in mean absolute coronary artery diameter, from 4.36 +/- 1.60 mm at baseline to 3.67 +/- 1.49 mm (16%) at 10 minutes and to 3.63 +/- 1.49 mm (17%) at 30 minutes after injection. There were no clinical sequelae. CONCLUSIONS Sumatriptan, a 5HT1 receptor agonist administered by the subcutaneous route, causes a vasopressor response in the systemic and pulmonary arterial circulations and coronary artery vasoconstriction.
Lewis A. Conner Lecture. Contributions of epidemiology to the prevention of stroke.
Authors: P A Wolf
Journal: Circulation (1993)

E pidemiological study and clinical trial research has flourished during the past 40 years.During this period the decline in death rates from stroke in the United States has accelerated.Since 1970 the US stroke mortality rate has declined nearly 60%.There is reason to believe the declining death rate is related to improvements in the risk factor status of the US population.Some of the data presented is derived from the Framingham Study and has been collected by many investigators during the past 40 years.I specifically acknowledge the contributions of
Pioneer Microbiologist: George Miller Sternberg
Authors: W. D. TIGERTT
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 August 1987Pioneer Microbiologist: George Miller SternbergW. D. TIGERTT, M.D.W. D. TIGERTT, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-2-265_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Operating under a need to be highly selective, Dr. Kass, in his recent article on the development of the speciality of infectious diseases in the United States (1), takes particular account of the contributions made in the early microbiologic era by George Miller Sternberg. Sternberg was probably the most influential microbiologist of his time; some details of his career are included in the body of the text and in a footnote. In the latter, probably by alapsus calami, Kass states that Sternberg founded the Army Medical Corps. Kass meant, I think, to recognize one of Sternberg's...References1. KASS E. History of the speciality of infectious diseases in the United States. Ann Intern Med. 1987;106:745-56. LinkGoogle Scholar2. General Orders No. 51, Headquarters of the Army, Adjutant General's Office, Washington, D.C., June 24, 1893. Cited from: Report of the Surgeon General of the Army to the Secretary of War for the Fiscal Year ending June 30, 1893. Washington, D.C.: Government Printing Office;1893:14. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1987Volume 107, Issue 2Page: 265-265KeywordsInfectious diseases Issue Published: 1 August 1987 PDF DownloadLoading ...
SOME THEORETICAL ASPECTS OF COLLAPSE THERAPY
Authors: F. H. Young
Journal: BMJ (1934)

TMTEBRJITTSR 66! to an excessive secretion of the intrinsic factor by the stomach, or to hypersusceptibility of the marrow to it, has been mooted by Morris.5 Whether phenylhydrazine might have some inhibitory or destructive effect on the intrinsic factor, or on the cells producing it, has not been suggested.
The <i>BMJ</i> interview: Sir Liam Donaldson: Avoiding the painful truth and scapegoats
Authors: Daniel McQueen
Journal: BMJ (2006)

EDITOR—I write with reference to the BMJ interview with the chief medical officer, Sir Liam Donaldson.1 I do not support his proposal that the standard of proof should be the civil standard when adjudicating about a doctor's performance.2

The individual doctor is the natural target when things go wrong and someone is needed to carry the blame, but this is scapegoating. …
Whatever Happened to the "Old-Time" Infections
Authors: Louis Weinstein
Journal: JAMA (1974)

REMARKABLE changes in the incidence and clinical features of some of the "old-time" infections have occurred over the past 25 to 30 years. Some of these have obviously been attributable to advances in prevention and treatment. For others, however, there are currently no discernible reasons for the alterations in their natural history. Although these changes have been taking place in all areas of our country, as well as in other developed parts of the world, this has not been the case in newly developing countries. The purpose of this article is to discuss this phenomenon, using data for incidence and personal experiences in Massachusetts since these reflect, in all probability, the situation in all areas of the United States. <h3>Varicella, Measles, and Poliomyelitis</h3> Varicella, measles, and poliomyelitis were very common in Massachusetts between 1945 and 1950. The total numbers of cases reported were 177, 761, 270, 675, and 10,181, respectively.
Correction: Sulfasalazine Dose
Authors: JEAN-PIERRE RAUFMAN
Journal: Annals of Internal Medicine (1985)

Letters and Corrections1 January 1985Correction: Sulfasalazine DoseJEAN-PIERRE RAUFMAN, M.D.JEAN-PIERRE RAUFMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-1-139_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I would like to bring to your attention an error in sulfasalazine dosing in the article by Peppercorn (1). On page 384, the article reads "These authors now advocate discontinuance of sulfasalazine treatments for 1 to 2 weeks in patients who have nausea, vomiting, abdominal pain, headache, reticulocytosis, and mild rash; treatment then can be restarted at a dose of 0.125 to 0.25 g/d for 1 week, with a gradual increase by 0.125 g/wk to a maintenance dose of 2 g/wk." The doses given as g/wk should both read g/d with substitution of the word weekly for...Reference1. PEPPERCORN M. Sulfasalazine: pharmacology, clinical use, toxicity, and related new drug development. Ann Intern Med. 1984;101:377-86. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Downstate Medical Center State University of New York Brooklyn, NY 11203 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1985Volume 102, Issue 1Page: 139-139KeywordsAbdominal painHeadachesNauseaPatient advocacyRashesVomiting Issue Published: 1 January 1985 PDF DownloadLoading ...
Vaccinate boys as well as girls against HPV: it works, and it may be cost effective
Authors: G. Prue
Journal: BMJ (2014)

<h3>ABSTRACT</h3> Intra-tumor heterogeneity in lymphoid malignancies is articulated around several fundamentals, encompassing selection of genetic subclonal events and epigenetic regulation of transcriptional programs. Clonally-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-intrinsic mesenchymal determinants impact on the diversification of aggressive lymphomas is still unknown. In this study we adopted the established A20 line-based model of Diffuse Large B-cell Lymphoma (DLBCL), to investigate the intra-tumor heterogeneity associated with the infiltration of different tissue microenvironments and the specific mesenchymal modifications that characterize stromal adaptation to lymphoma seeding. Combining <i>in situ</i> quantitative immunophenotypical analyses and RNA sequencing, we found that the tissue microenvironment casts a relevant influence over A20 transcriptional landscape also impacting on Myc and DNA damage response programs. Extending the investigation to mice deficient for the matricellular protein Sparc, a stromal determinant endowed with a strong prognostic significance in human DLBCL, we demonstrated a different immune imprint on A20 cells related to stromal <i>Sparc</i> proficiency. The study provides the first evidence of human DLBCL intra-lesional heterogeneity arising from diversified mesenchymal contextures and impacting on MYC expression, advancing the challenge for resolving intra-tumor heterogeneity probing stromal/immune interfaces. <h3>KEY POINTS</h3> Diversified stromal adaptations of infiltrated tissues shape DLBCL intra-tumor heterogeneity regulating transcriptional/phenotypic features Stromal Sparc, which endorses prognostic significance in DLBCL, tunes the immune pressure exerted on lymphoma cells by the microenvironment
Lung Cancer: Perspectives and Prospects
Authors: PAUL P. CARBONE
Journal: Annals of Internal Medicine (1970)

Lung cancer offers a challenge for earlier diagnosis and better treatment results. At present lung cancer is recognized late. Opportunities to improve survival are through early detection, accurate diagnosis, absolute localization, and curative therapy. Improvements in diagnosis are being developed, including the fibro-optic bronchoscope. The biology of lung cancer is reflected by its morphological characteristics and clinical symptoms. A clinicoanatomic scheme permits prediction of survival. Surgical treatment remains the only definitive cure. A large study (VA Surgical Adjuvant Group) has indicated no improvement in survival with short-term adjuvant chemotherapy or preoperative X-ray therapy At present treatment with intermittent long-term therapy is administered in hopes of decreasing recurrence rates. The VA Lung Cancer Medical Group has shown improved survival with mechlorethamine in squamous cell carcinoma and cyclophosphamide in oat cell carcinoma. Future advances would include use of combinations of drugs. Prospects for patients should improve soon because of leads presented in this conference.
GMC changes verdict after rehearing neurosurgeon's case
Authors: C. Dyer
Journal: BMJ (2009)

<h3>Abstract</h3> Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition occurring in individuals exposed to trauma. The study of PTSD is complicated by highly heterogeneous presentations and experiences of trauma. Here, we studied genetic correlates of PTSD and resilience among a group of responders to the World Trade Center (WTC) 9/11/2001 attacks. This cohort represents a unique opportunity to study genetic risk factors for PTSD, and resilience, following a single, shared, well-documented trauma. We calculated polygenic risk scores associated with PTSD among these 375 individuals, and demonstrated a significant genetic association with social cognition traits, brain volumetric phenotypes, and PTSD-GWAS-derived PRS. Our results demonstrate significant genetic regulation of PTSD severity (CAPS scores) and chronicity (past-month CAPS). PRS derived from GWAS of ADHD, ASD, and brain imaging phenotypes (Amygdala and Putamen volume) were associated with multiple PTSD traits in this study. Interestingly, we find greater genetic contribution to PTSD among cases compared to our full cohort. In addition, we tested for associations between exposures to traumatic stressors, including WTC-related exposures, childhood trauma, and traumatic life events since 9/11. Together, polygenic risk and exposures to traumatic stress explain ∼45% of variance in lifetime CAPS among the full cohort (R<sup>2</sup>=0.454), and ∼48% of variance in past-month CAPS (R<sup>2</sup>=0.480). These participants represent a highly vulnerable population, with exposures to severe trauma during 9/11 and the following days. Identifying individuals at heightened risk for PTSD, or who may be suited to particular therapies, is of special importance and relevance in this group. In particular, the identification of MRI imaging phenotypes indicates that coupling of neuroimaging with genetic risk score calculations may predict PTSD outcomes.