tbuckley/cabot-search huggingface dataset:
Abstract IA12: Long-range gene regulation in the context of chromatin domains
Authors: Job Dekker
Journal: Cancer Research (2016)

Abstract The 3D organization of the genome is critical for gene regulation, genome stability and faithful transmission of chromosomes to daughter cells. We apply Chromosome Conformation Capture-based technologies to determine how cells fold their chromosomes and to discover the mechanisms that drive the spatial organization of genomes. I will discuss our recent proposal that in interphase nuclei mammalian chromosomes are hierarchically organized (Gibcus and Dekker, 2013). First, at the nuclear level, chromosomes are compartmentalized into large multi-Mb domains that are either active and open or inactive and closed. These compartments themselves are composed of smaller sub-Mb Topologically Associating domains (TADs) (Dixon et al. 2012, Nora et al. 2012). Finally, long-range gene regulation occurs within TADs through long-range looping interactions between genes and regulatory elements. TAD organization and their role in gene regulation have important implications in cancer cells. I will highlight how genomic rearrangements in cancer genomes can lead to altered TAD organization and inappropriate gene expression, including increased expression of cancer promoting genes, and repression of cancer suppressing genes. I will also highlight two new studies from my laboratory that reveal different roles of TADs in chromosome-wide gene regulation along the dosage compensated X-chromosomes. First, in C. elegans we find that a Condensin complex mediates TAD formation and dosage compensation. Second, in mouse the dosage compensated X chromosome folds in a unique way with global loss of TADs. Citation Format: Job Dekker. Long-range gene regulation in the context of chromatin domains. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr IA12.
Pheochromocytoma Is Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, and Myocardial Dysfunction
Authors: Vanessa M. Ferreira, Mafalda Marcelino, Stefan K. Piechnik, Claudia Marini, Theodoros D. Karamitsos, Ntobeko A.B. Ntusi, Jane M. Francis, Matthew D. Robson, J. Ranjit Arnold, Radu Mihai, Julia D.J. Thomas, Maria Herincs, Zaki K. Hassan-Smith, Andreas Greiser, Wiebke Arlt, Márta Korbonits, Niki Karavitaki, Ashley B. Grossman, John A.H. Wass, Stefan Neubauer
Journal: Journal of the American College of Cardiology (2016)

Pheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. This study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). A total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]). Patients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups. This first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations.
RE: Germline Mutations in Shelterin Complex Genes Are Associated With Familial Glioma
Authors: J. G. Cooke
Journal: JNCI Journal of the National Cancer Institute (2015)

The title of the paper by Bainbridge et al. (1) is an assertion that is not supported by the evidence presented. A genetic mutation is (positively) associated with a disease when a carrier of the mutation is more likely to contract the disease than a noncarrier or (equivalently) when a sufferer of the disease is more likely to carry the mutation than a nonsufferer. The results of the Bainbridge et al. study do not indicate an association.

The authors conducted whole-exome sequencing on 90 individuals from 55 families with a history of glioma and selected variants that were shared among two or more individuals diagnosed with glioma within a family. Two variants meeting these criteria were found, both in the POT1 gene. The authors went on to sequence the POT1 gene from a further 264 glioma patients. The two variants identified in the initial sample were not found in any individuals in the second sample. However, one patient was found in the second sample with a third variant in the same gene.

Normally, a scientific study involves forming a provisional hypothesis based on some data and then examining further data to see whether or not they support the hypothesis. The finding that no individuals in the second sample carried the variants identified in the first sample represents lack of support for the hypothesis that these variants are associated with glioma.

If the hypothesis being advanced is not just about the two variants found in the first sample, but is a more general hypothesis that mutations in POT1 are associated with glioma, then the data also fail to support it. The occurrence of a POT1 mutation in one patient out of 264 in the confirmatory sample is no more than would be expected by chance given the background occurrence of approximately 1% as indicated by the 65 nonsynonymous POT1 mutations found in the 6200 individuals of the control sample.

The occurrence of POT1 mutations in glioma sufferers in two families of the initial sample of 55 families does not represent evidence for an association, because the POT1 gene was singled out (out of a not precisely specified, but potentially quite large, pool of candidate genes) on the basis of mutations in this gene being carried by multiple glioma sufferers within a family in this particular sample of families.

Hunting for genetic risk factors in cancers is a fast-expanding field, and findings of “associations” are sometimes published before applying statistical logic to the evidence. It is troubling that the authors suggest that individuals with a family history of glioma should undergo screening for mutations in POT1. In the absence of evidence that such mutations confer an elevated risk of contracting glioma, such screening could cause some expense and much anxiety without an accompanying benefit.
RADIOGRAPHY WITH RADIOACTIVE ISOTOPES
Authors: H J IRELAND
Journal: JAMA (1952)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Preparation of Membrane Fractions With Enhanced Tumor-Transplantation-Antigen Activity From Tumor Cells Infected With Influenza Virus
Authors: Charles W. Boone, Thomas W. Orme, Kenneth Blackman, Ronald Gillette
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Preparation of Membrane Fractions With Enhanced Tumor-Transplantation-Antigen Activity From Tumor Cells Infected With Influenza Virus Get access Charles W. Boone, Charles W. Boone 2Cell Biology Section, Viral Biology Branch, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health. Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas W. Orme, Thomas W. Orme 2Cell Biology Section, Viral Biology Branch, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health. Education, and Welfare, Bethesda, Md. 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth Blackman, Kenneth Blackman 3Meloy Laboratories, Springfield, Va. 22151 Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald Gillette Ronald Gillette 3Meloy Laboratories, Springfield, Va. 22151 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 4, October 1973, Pages 1141–1144, https://doi.org/10.1093/jnci/51.4.1141 Published: 01 October 1973 Article history Received: 18 January 1973 Accepted: 11 May 1973 Published: 01 October 1973
Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age
Authors: Gayan Bowatte, Caroline J. Lodge, Luke D. Knibbs, Adrian J. Lowe, Bircan Erbas, Martine Dennekamp, Guy B. Marks, Graham Giles, Stephen Morrison, Bruce Thompson, Paul S. Thomas, Jennie Hui, Jennifer L. Perret, Michael J. Abramson, Haydn Walters, Melanie C. Matheson, Shyamali C. Dharmage
Journal: Journal of Allergy and Clinical Immunology (2016)
Aftermath of the Rogers decision: assessing the costs
Authors: R Schouten, T G Gutheil
Journal: American Journal of Psychiatry (1990)

The Massachusetts Supreme Judicial Court's decision in Rogers v. Commissioner is generally regarded as an important right to refuse treatment decision requiring maximum judicial involvement in the treatment of nonconsenting patients. Since courts and legislators in other jurisdictions have looked to Rogers for guidance on right to refuse treatment issues, and since some have adopted it as a model, it is essential for lawmakers to understand the economic realities of the Massachusetts experience and the commitment of resources required by this model. The authors review these realities, suggesting that there are distinct reasons for considering this particular model "cost ineffective" in preserving patients' rights.
Some Aspects of “Hepatoma NK”&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;
Authors: A B NOVIKOFF
Journal: JNCI Journal of the National Cancer Institute (1955)

Journal Article Some Aspects of “Hepatoma NK” Get access Alex B. Novikoff Alex B. Novikoff Waldemar Medical Research Foundation, Port Washington, N. Y Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue Supplement_5, April 1955, Pages 1533–1534, https://doi.org/10.1093/jnci/15.Supplement_5.1533 Published: 01 April 1955
Abstract B28: PTENpg1 antisense RNA mediates PTEN suppression in vemurafenib resistance and predicts clinical outcome in melanoma patients
Authors: Linda Vidarsdottir, Alireza Azimi, Jason Serviss, Christian Ingvar, Göran Jönsson, Håkan Olsson, Marianne Frostvik Stolt, Johan Hansson, Suzanne Egyházi Brage, Dan Grandér, Per Johnsson
Journal: Cancer Research (2016)

Abstract Approximately 50% of cutaneous melanomas carry activating mutations in the serine/threonine protein kinase BRAF. Vemurafenib is a highly potent inhibitor of BRAFV600E and prolongs survival in ~80% of melanoma patients carrying the mutation. Unfortunately, almost all patients develop resistance within 6-8 months of starting treatment. The molecular mechanism explaining this scenario is largely unclear, but loss of PTEN expression, has been suggested. In this study we reveal a role for the PTEN pseudogene encoded antisense RNA (PTENpg1 asRNA) in epigenetic suppression of PTEN in melanoma cell lines resistant to vemurafenib. Resistant cell lines showed increased PTENpg1 asRNA expression while PTEN expression was suppressed. ChIP analysis showed enrichment of the histone modification enzyme EZH2 and subsequent enrichment of H3K27me3 at the PTEN promoter in the resistant cell line. Total cellular levels of EZH2, DNMT3a and H3k27me3 were, however, unaffected thus indicating specific recruitment of these factors to the PTEN promoter in the resistant cells by a mechanism that is dictated by the increased expression of PTENpg1 asRNA. In addition, we show that PTEN is reactivated by the depletion of EZH2 and DNMT3a and that this reactivation of PTEN re-sensitizes the cells to vemurafenib treatment. Finally, we show that PTENpg1 asRNA could be a promising prognostic marker of clinical outcome of melanoma patients. PTENpg1 asRNA expression levels were measured in samples from patients that had not received any oncological treatment and were classified with stage III melanomas. We found that high PTENpg1 asRNA expression correlates with short-term survival in melanoma patients. In conclusions, the PTENpg1 asRNA appears to be an important player in vemurafenib resistance and could be an attractive therapeutic target. In addition, PTENpg1 asRNA is potentially a promising prognostic marker for clinical outcome for melanoma patients. Citation Format: Linda Vidarsdottir, Alireza Azimi, Jason Serviss, Christian Ingvar, Göran Jönsson, Håkan Olsson, Marianne Frostvik Stolt, Johan Hansson, Suzanne Egyházi Brage, Dan Grandér, Per Johnsson. PTENpg1 antisense RNA mediates PTEN suppression in vemurafenib resistance and predicts clinical outcome in melanoma patients. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B28.
Postthrombotic Syndrome
Authors: Sara R. Vazquez, Susan R. Kahn
Journal: Circulation (2010)

P ostthrombotic syndrome (PTS) is a problem that can develop in nearly half of all patients who experience a deep vein thrombosis (blood clot) in the leg. 1,2PTS symptoms include chronic leg pain, swelling, redness, and ulcers (sores).It can be expensive to treat and make it difficult for you to get around, and the pain and discomfort can make your life less enjoyable.The best thing to do is to prevent this problem whenever possible.
Combined treatment with the LHRH-agonist buserelin (LHRH-A) and tamoxifen (TAM) vs single treatment with each drug alone in premenopausal metastatic breast cancer. Final results of EORTC study 10881
Authors: Jgm Klijn, L Beex, L Mauriac, J Van Zijl, C Veyret, J Wildiers, J Jassem, J Burghouts, M Piccart, F Mignolet, Luc Duchateau
Journal: Annals of Oncology (1998)
Angiosarcoma of the Liver: An Epidemiologic Survey2
Authors: Judith Brady, Florinda Liberatore, Philip Harper, Peter Greenwald, William Burnett, J. N. P. Davies, Monica Bishop, Adele Polan, Nicholas Vianna
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Angiosarcoma of the Liver: An Epidemiologic Survey Get access Judith Brady, B.S., Judith Brady, B.S. Search for other works by this author on: Oxford Academic PubMed Google Scholar Florinda Liberatore, Florinda Liberatore Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip Harper, B.S., Philip Harper, B.S. Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Greenwald, M.D., Peter Greenwald, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar William Burnett, M.D., William Burnett, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. N. P. Davies, M.D., J. N. P. Davies, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Monica Bishop, M.D., Monica Bishop, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Adele Polan, M.A., Adele Polan, M.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicholas Vianna, M.D. Nicholas Vianna, M.D. 7 7Address reprint requests to Dr. Nicholas Vianna. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 5, November 1977, Pages 1383–1385, https://doi.org/10.1093/jnci/59.5.1383 Published: 01 November 1977 Article history Received: 18 February 1977 Accepted: 13 June 1977 Published: 01 November 1977
PSYCHOANALYTIC TRAINING FOR PSYCHIATRIC RESIDENTS AND OTHERS
Authors: HENRY W. BROSIN
Journal: American Journal of Psychiatry (1952)

1. Attention is called to various types of residency training involving several educational groups. 2. The growth and goals of the Associated Psychiatric Faculties of Chicago are described briefly. 3. The importance of selection is stressed and the experiment in group interviewing presented. Improved criteria for more specific selection are being developed. An enlarged concept of responsibility to students is vital. They should receive much more guidance and direction so that they may be spared unnecessary hardships. The training (preparatory) analysis itself is probably the best means of selection if training groups could act on their own findings. 4. The need for more and better training facilities through building up " city-wide interinstitutional" medical centers is presented so that training may be provided for nonpsychiatrists as well as psychiatrists at all levels. 5. The need for more training and interest in investigation is emphasized. The advantages of university affiliations to promote these objectives seem apparent.
Website of the week: Specialists and generalists
Authors: Douglas Carnall
Journal: BMJ (2000)

In Britain most people recognise that we need both specialist and generalist physicians because patients refuse to specialise, often having the temerity to complain of problems that transgress specialty boundaries. In this week's BMJ two articles attempt a modern definition of the general practitioner, which in many countries means merely “not a specialist.”

Problems of definition can often be resolved by recourse to a dictionary, and WordNet (www.cogsci.princeton.edu/∼wn/) has the kind of information that the impulsive generalist cannot resist: it indexes “lexical concepts” inspired by “current psycholinguistic theories of human lexical memory.” Its definition of a generalist is “a Renaissance man ... who is in a position to acquire more than superficial knowledge about many different interests.” Apart from an embarrassment of sexist language, that seems a fair definition of the opportunities afforded in general practice.

The concept that stalks all such debates is the self esteem of the discipline; those who have concerned themselves with the issues for long enough usually seem to argue for a separate specialty with its own assessments. Validating these qualifications across Europe is the job of the European Union: at http://citizens.eu.int/ professionals can enter their country of origin and their planned destination, then download relevant information for the transition.

It is not just medicine that grapples with the generalist-specialist problem: at http://home.att.net/[]nickols/general.htm, Nickols argues that the virtue of the generalist is to have integrated several specialties, and that, having integrated them, is more able to bend that knowledge to the needs of the client. The opposite, he rather contentiously suggests, is for the specialist to insist that the client needs what the specialist does. But we wouldn't have that sort of thing in medicine, would we?
Stroma-Contact Prevents Loss of Hematopoietic Stem Cell Quality During Ex Vivo Expansion of CD34+ Mobilized Peripheral Blood Stem Cells
Authors: Dimitri A. Breems, Ellen A.W. Blokland, Karen E. Siebel, Angelique E.M. Mayen, Lilian J.A. Engels, Rob E. Ploemacher
Journal: Blood (1998)
On the Immediate Treatment of Stricture of the Urethra
Authors: B. Holt
Journal: BMJ (1862)

elevation witlh its long axis horizontal.The iris was much obscured by blood in its anterior chanmber.Mlay 14th.. Some of the effused blond having been absorbed,the oval elevation above named was seen to be the dislocated lens.The iris was found to be ruptured at its upper and inner part, and one-thircd of it to be deficient.