tbuckley/cabot-search huggingface dataset:
MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis
Authors: Atsushi Terunuma, Nagireddy Putluri, Prachi Mishra, Ewy A. Mathé, Tiffany H. Dorsey, Ming Yi, Tiffany A. Wallace, Haleem J. Issaq, Ming Zhou, J. Keith Killian, Holly S. Stevenson, Edward D. Karoly, King Chan, Susmita Samanta, DaRue Prieto, Tiffany Y.T. Hsu, Sarah J. Kurley, Vasanta Putluri, Rajni Sonavane, Daniel C. Edelman, Jacob Wulff, Adrienne M. Starks, Yinmeng Yang, Rick A. Kittles, Harry G. Yfantis, Dong H. Lee, Olga B. Ioffe, Rachel Schiff, Robert M. Stephens, Paul S. Meltzer, Timothy D. Veenstra, Thomas F. Westbrook, Arun Sreekumar, Stefan Ambs
Journal: Journal of Clinical Investigation (2013)

Metabolic profiling of cancer cells has recently been established as a promising tool for the development of therapies and identification of cancer biomarkers. Here we characterized the metabolomic profile of human breast tumors and uncovered intrinsic metabolite signatures in these tumors using an untargeted discovery approach and validation of key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human breast cancer cell lines. We discovered an association between increased 2HG levels and MYC pathway activation in breast cancer, and further corroborated this relationship using MYC overexpression and knockdown in human mammary epithelial and breast cancer cells. Further analyses revealed globally increased DNA methylation in 2HG-high tumors and identified a tumor subtype with high tissue 2HG and a distinct DNA methylation pattern that was associated with poor prognosis and occurred with higher frequency in African-American patients. Tumors of this subtype had a stem cell–like transcriptional signature and tended to overexpress glutaminase, suggestive of a functional relationship between glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our findings implicate 2HG as a candidate breast cancer oncometabolite associated with MYC activation and poor prognosis.
Anti-helminth treatment lead to a reduction on asthma severity
Authors: M. Medeiros, M.C.F. Almeida, A.A. Cruz, J.P. Figueiredo, R.R. Oliveira, L.M. Alcantara, C.B. Aquino, E.M. Carvalho, M.I. Araujo
Journal: Journal of Allergy and Clinical Immunology (2005)
A Correction in Paul's A History of Poliomyelitis
Authors: JOSEPH STOKES
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 May 1972A Correction in Paul's A History of PoliomyelitisJOSEPH STOKES JR., M.D.JOSEPH STOKES JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-828_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAs an old friend of the late Dr. Paul it is disturbing to have to correct any item of fact in so splendid a history of poliomyelitis (1) as he has compiled. When the error concerns an important rung in the ladder of knowledge leading to the control of poliomyelitis, however, I have been advised by many other mutual friends that it should receive a short note.The correction of the mistake changes an opinion mentioned in his history from a subjective one to an objective one. The story involves the field studies of the control of poliomyelitis by gamma...References1. PAUL J: A History of Poliomyelitis. New Haven, Yale University Press, 1971, p. 394 Google Scholar2. STOKES J: Thayer Lectures I and II. Johns Hopkins Med J 121:305-328, 1967 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: The Henry Phipps Institute Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 828-828KeywordsPoliomyelitis Issue Published: 1 May 1972 PDF downloadLoading ...
Defective colour vision in diabetes: a hazard to management.
Authors: D G Thompson, F Howarth, H Taylor, I S Levy, J Birch
Journal: BMJ (1979)

laparotomyl or were examined post mortem.13 14An appreciable proportion of patients, however-140, in the Public Health Laboratory Service series9-had fresh blood, pus, or mucus in their stools, suggesting colorectal inflammation.The presence of proctitis in eight of the 11 patients in the present series suggested that colonic inflammation occurred commonly in those patients whose symptoms were severe enough to require hospital admission, and may have played an important part in producing the diarrhoea.It is accepted that infection with salmonella, shigella, or amoeba should be included in the differential diagnosis of irritable bowel disease, and our findings indicate that campylobacter should be considered.The changes seen on sigmoidoscopy and with a barium enema have little value in differentiating campylobacter colitis from irritable bowel disease, and, moreover, the histology of rectal biopsy specimens may show changes of this disease, thus compounding the problem.The importance of comprehensive bacteriological studies in all patients presenting with bloody diarrhoea cannot be overemphasised.Patients who in the past were diagnosed as having irritable bowel disease on clinical, sigmoidoscopic, and histological grounds may well have been suffering from unrecognised campylobacter colitis.
GMC calls for greater safeguards when doctors and patients move across EU borders
Authors: C. Dyer
Journal: BMJ (2008)

A new draft directive from the European Commission giving patients the right to access treatment in other European Union member states ( BMJ 2008;337:a676, 3 Jul, doi: 10.1136/bmj.a676) must be accompanied by greater safeguards for patients, the General Medical Council says.

The GMC, the regulatory body for doctors in the United Kingdom, is calling for firmer legal duties on regulators across the European Union to share information, test doctor’s language competence, and create mechanisms to ensure that doctors’ performance and competence are acceptable.

It said that the draft directive on patients’ rights in cross border health care “potentially represents a significant change in access to and delivery of healthcare across Europe” …
ANATOMIC DIAGNOSIS OF INJURIES OF THE HAND
Authors: JAMES M. WINFIELD
Journal: JAMA (1941)

As has been so aptly stated by Kanavel, "The hand of the working man is his most valuable asset. Without it life becomes a burden."<sup>1</sup>Appreciating this, the surgeon when caring for an injured hand must exert the utmost diligence in making a correct diagnosis, in performing careful and expert treatment and in carrying out meticulous after-care. Although the hazards of industry have been materially reduced, physicians are still faced with the problem of treating great numbers of injuries to the hand. Before any active treatment of such wounds is undertaken it is paramount that an exact diagnosis be made and a careful analysis made as to the cause, location and extent of the lesion. It may seem almost unnecessary to emphasize the importance of this initial procedure, but so often if it is neglected or carelessly performed a finger or hand may be rendered useless or a life
Improvised Iron Lung
Authors: A. J. Murray
Journal: BMJ (1956)

Infective Nature of Massive Pneumoconiosis SIR,-J,t is believed in the Welsh National School of Medicine, Cardiff, that coal-miners' pneumoconiosis is of two distinct pathological types.'Simple pneumoconiosis is thought to be due to dust alone and massive fibrosis to dust plus infection.Tuberculosis is regarded as being the
Antenatal screening for cystic fibrosis: a trial of the couple model
Authors: J Livingstone, R A Axton, A Gilfillan, M Mennie, M Compton, W A Liston, A A Calder, A J Gordon, D J H Brock
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To assess the delivery and acceptability of antenatal couple screening for cystic fibrosis. Carrier status was notified only when both members of a partnership had cystic fibrosis alleles and therefore a one in four risk of having an affected child. <b>Design</b>: Mouthwash samples were tested when both partners participated. Results were returned only to positive couples. <b>Setting</b> : Two large maternity hospitals in Edinburgh. <b>Subjects</b> : Screening was offered to all couples who booked at one of the two hospitals. <b>Main outcome measures</b> :(a) The take up of screening, carriers and carrier couples identified, take up of prenatal diagnosis, and numbers of affected fetuses detected; (b) questionnaire measures of patient satisfaction and stress. <b>Results</b> : Screening was offered to 8536 couples. 714 (8.4%) were regarded as ineligible, usually because of late booking or absence of a partner. 1900 (24.3%) of the remainder declined screening. Among the 5922 screened couples, four tested positive - that is, both partners were cystic fibrosis heterozygotes. All four elected to have prenatal diagnosis. There were three terminations of pregnancy because of an affected fetus, one couple having two successive pregnancies with affected fetuses. The participation rate was 76% for eligible couples (5922/7822) and 69% for all couples (5922/8536). Only 89 screened couples (1.5%) requested information on individual carrier status. No anxiety was detected among a cohort of the screened population, and 99% of questioned participants expressed satisfaction with the concept of couple screening. <b>Conclusions</b> : Antenatal couple screening is a20satisfactory and acceptable way of screening for cystic fibrosis and has been adopted as routine in the two trial hospitals.
Interpreting Plasma Estrogen Levels in Breast Cancer: Caution Needed
Authors: Elizabeth J. Folkerd, Per E. Lønning, Mitch Dowsett
Journal: Journal of Clinical Oncology (2014)

Plasma estrogen levels have been measured in many research studies and have been used to direct clinical management in patients with breast cancer. When used with samples from postmenopausal women, most assays are not adequately accurate for this purpose, and unfortunately there are few available assays that do have the required accuracy and precision. Authors and reviewers have failed to recognize that using the wrong assays has led to clearly inaccurate data in some recently published studies. This situation needs to be recognized promptly to avoid reinforcing incorrect interpretations that may affect clinical care. Errors resulting from this inaccuracy can lead to real harm and may affect large numbers of women because of the prevalence of estrogen receptor–positive (ER ) breast cancer, which results in many patients receiving endocrine therapy. This article reviews areas in which estrogen measurements are made in relation to breast cancer and highlights the dangers of erroneous measurement or interpretation.
A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling
Authors: Katherine Bessette, Mark L. Lang, Roy A. Fava, Martin Grundy, Jennifer Heinen, Laurie Horne, Rosanne Spolski, Amin Al-Shami, Herbert C. Morse, Warren J. Leonard, John A. Kelly
Journal: Blood (2007)
The Huxley Lecture on Recent Advances in Science, and their Bearing on Medicine and Surgery: Delivered at Charing Cross Hospital Medical School on October 5th, 1896
Authors: M. Foster
Journal: BMJ (1896)

<h3>Aim</h3> Medical leadership and management (LM) is recognised as an essential facet of clinical practice; poor LM leads to poor patient outcomes. However, there lacks standardised, sustainable training for all clinical professions whilst clinician burnout, and associated risks of increased patient safety incidents, is a national concern. Through the Government Apprenticeship Scheme NHS Trusts have access to a ring-fenced budget that can provide funded, vocationally based, nationally benchmarked leadership and management (LM) training which can support staff LM development. <h3>Methods</h3> In December 2017, through a partnership between the authors, South Tees Hospitals NHS Foundation Trust (STEES) and Always Consult, a Registered Apprenticeship Training provider, the Foundation Leadership and Management (FLM) programme for Foundation Year 1 doctors (FY1s) was launched. Believed to be the first clinical LM Apprenticeship in the United Kingdom, FLM is mapped to the FY1 clinical curriculum and leads to a nationally recognised qualification enabling membership of two leading international LM bodies. FLM has been shown to increase FY1s’ preparedness for the LM challenges of practice and resilience. <h3>Results</h3> FLM’s clinical LM Apprenticeship concept was used by STEES in 2018 to create a Ward Managers’ programme; further programmes for Allied Healthcare Professionals, Consultants, Matrons, Staff Grade Nurses and Trust Grade Doctors are planned. Other healthcare organisations, using the FLM concept, are currently preparing to launch clinical LM Apprenticeships including Health Education North East’s programme for Acute Care Common Stem Trainees. <h3><b>Conclusion</b>s</h3> Clinical LM Apprenticeship programmes, such as FLM, can increase staff self-rated LM preparedness and resilience. Apprenticeships offer an opportunity to establish locally deliverable LM programmes, for all professions and levels, which holistically benefit staff in a resource constrained and challenging environment.
Induction of mutation spectra by complex mixtures: approaches, problems, and possibilities.
Authors: D M DeMarini
Journal: Environmental Health Perspectives (1994)

More complex environmental mixtures have been evaluated for mutagenic activity at the hisD3052 allele of Salmonella, primarily in strain TA98, than in any other target or mutation assay. Using colony probe hybridization to detect a common hot spot deletion, followed by polymerase chain reaction and DNA sequencing, we have generated 10 mutation spectra from three classes of mixtures (i.e., urban air, cigarette smoke condensate, and municipal waste incinerator emissions). The mutation spectra are distinctly different among the three classes of mixtures; however, the spectra for samples within the same class of mixture are similar. In addition to the hot spot mutation, the mixtures induce complex mutations, which consist of a small deletion and a base substitution. These mutations suggest a mechanism involving misinsertion of a base opposite a DNA adduct followed by a slippage and mismatch. A role for DNA secondary structure also may be the basis for the mutational site specificity exhibited by the various mixtures. The results suggest that unique mutation spectra can be generated by different classes of complex mixtures and that such spectra are a consequence of the dominance of a particular chemical class or classes within the mixture. The problems associated with this type of research are discussed along with the potential value of mutation spectra as a tool for exposure and risk assessment.
A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets
Authors: Dafydd H. Thomas, Todd M. Getz, Tiffanny N. Newman, Carol A. Dangelmaier, Nick Carpino, Satya P. Kunapuli, Alexander Y. Tsygankov, James L. Daniel
Journal: Blood (2010)
Changes in collagen phenotypes during progression and regression of cardiac hypertrophy
Authors: Chun Mu Yang, Vijaya Kandaswamy, David Young, Subha Sen
Journal: Cardiovascular Research (1997)

Excessive deposition of collagen has been implied to be responsible for abnormal stiffness and altered cardiac function during hypertrophy and heart failure. In the present paper we studied the changes in collagen and their phenotypes during development of cardiac hypertrophy in spontaneously hypertensive rats (SHR) compared to age- and sex-matched Wistar Kyoto (WKY). We also studied the changes in collagen after regression of hypertrophy, with antihypertensive therapy with ACE inhibitors, captopril (C) and lisinopril (L).Collagen was extracted from the heart tissue by cyanogen bromide (CNBr) digestion. Collagen phenotypes were separated and quantified by SDS-polyacrylamide gel electrophoresis. The transcript levels(mRNA) of collagen phenotypes were determined by Northern analysis.Our studies showed that the ventricular collagen and their phenotypes did not alter in SHR during the first 6 months of progression of hypertrophy when compared to WKY. After 40 weeks, however, in SHR there was an unexpected rise in collagen content and the distribution of collagen phenotype differs compared to WKY, especially during the chronic phase of hypertrophy (65 weeks of age). In WKY during the aging process there was a gradual increase in type III collagen, whereas in SHR it plateaus after 40 weeks of age. Treatment with antihypertensive drugs captopril and lisinopril showed a similar degree of reduction in blood pressure (P < 0.001), regressed hypertrophy (P < 0.001), and reduced collagen, whereas decrease in type I to III ratio was found with captopril only, but not with lisinopril. This decrease in type I to III ratio due to captopril treatment is primarily due to an increase in type III collagen (both protein and transcript level) in SHR.Our data showed, for the first time, that during the chronic phase of hypertrophy in SHR there is a gradual reduction in type I to III ratio, primarily due to a lack of increase in type III collagen during chronic phase of hypertrophy. This suggests that quality of collagen is an important factor in determining the degree of cardiac stiffness. Our data also showed that not all ACE inhibitors have similar actions on collagen phenotype production. This suggests that perhaps the mechanism of action of ACE inhibitors on collagen are independent of its effect on angiotensin II formation.
Quantitation of thermography in arthritis using multi-isothermal analysis. I. The thermographic index.
Authors: A J Collins, E F Ring, J A Cosh, P A Bacon
Journal: Annals of the Rheumatic Diseases (1974)

Thermography can be used for the assessment of joint involvement in inflammatory arthritis.Modem thermographic apparatus allows temperature to be measured to within 0-2°C.and simultaneously records the areas involved.It has been demonstrated that thermographic changes in skin temperature over areas of chronic inflammation properly reflect changes in other chemical and cellular processes in rheumatoid arthritis (Ring and Collins, 1970;Collins and Cosh, 1970).The method also agrees with the findings of joint scans after technetium injection (Cosh, Lindsay, Rhys-Davies, and Ring, 1970) and correlates with the intra-articular temperature taken by thermistor probe (Lloyd-Williams, Ring, and Cosh, 1970).Recently Pinder and Ring (1974) have shown that thermographic recordings accurately locate areas of inflamed synovial tissue as shown at synovectomy.The effect of anti-inflammatory compounds on joint inflammation in animals has been quantitated using radiometry (Collins and Ring, 1972).Thermography provides more information about the distribution of temperature.We wish to report a method for the quantitative measurement of joint inflammation in man, using thermography.Method THERMOGRAPHIC APPARATUS
High-affinity T helper epitope induces complementary helper and APC polarization, increased CTL, and protection against viral infection
Authors: Jeffrey D. Ahlers, Igor M. Belyakov, Elaine K. Thomas, Jay A. Berzofsky
Journal: Journal of Clinical Investigation (2001)

Natural viral proteins do not always make optimal vaccines. We have found that sequence modification to increase epitope affinity for class II MHC molecules (epitope enhancement) can improve immunogenicity. Here we show first that a higher-affinity helper epitope-enhanced HIV vaccine not only induces more cytotoxic T lymphocytes (CTLs), but also skews helper cells toward Th1 cytokine production and protects against HIV-1 recombinant vaccinia viral challenge. Furthermore, we elucidate a novel mechanism in which the higher-affinity vaccine induces dramatically more effective helper cells with a higher level of CD40L per helper cell and more positive cells, which in turn more effectively conditions dendritic cells (DCs) for CTL activation in a second culture. The improved helper cells also induce much greater IL-12 production by DCs, accounting for the reciprocal T helper polarization to Th1, and increase costimulatory molecule expression. Thus, increasing affinity for class II MHC results in a complementary interaction in which T helper and antigen-presenting cells polarize each other, as well as increase CTL, and provide greater vaccine efficacy against viral infection.
Abstract 5273: The cyclin dependent kinase inhibitor p27KIP1 inhibits neuroblastoma cell migration and invasion
Authors: Dana-Lynn T. Koomoa-Lange, Andre S. Bachhmann
Journal: Cancer Research (2010)

Abstract Neuroblastoma (NB) is the most common extra-cranial pediatric tumor. Over 70% of NB patients are diagnosed with metastasis, and the survival probability of these patients is significantly lower than patients without metastasis. While the role of p27KIP1 in cell cycle regulation is well documented and conserved in all cell types, there are contradictory reports regarding its function in regulating cell migration and invasion. The purpose of the present study was to elucidate the role of p27KIP1 in regulating migration and invasion of NB cells with MYCN over-expression. Western blot analysis, migration and invasion assays were performed on NB cells with and without over-expression of MYCN. The expression of p27KIP1 was down-regulated using siRNA, and the migration rate was determined on NB cells with MYCN over-expression. Also, the cytoplasmic localization of p27KIP1 in NB cells with and without MYCN over-expression was determined. The results from the current study show that MYCN over-expression increases migration and invasion of NB cells, compared to cells without MYCN over-expression via a process that involves p27KIP1. In addition to its role as a cell cycle regulator, p27KIP1 also regulates NB migration and invasion. This dual role of p27KIP1 as a tumor repressor suggests that it may be an attractive therapeutic target for NB. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5273.
Psychiatric Care of Migrants: A Clinical Guide
Authors: Howard A. Winkler
Journal: JAMA (1990)

One of the most important elements in reviewing a nonfiction book is to determine if the author has accomplished his goal. Joseph Westermeyer in his book<i>Psychiatric Care of Migrants</i>fulfills my criterion with flying colors. That he spent considerable time in researching the title subject is amply demonstrated by the prodigious number of references at the conclusion of each chapter. Dr Westermeyer has broadened the definition of migrant, which to many has simply meant one who migrates, or a person who moves regularly to find work, especially in harvesting crops. He includes not only the typical migrant worker, but also students who go off to school, transferred or migratory workers, people whose work may necessitate travel, tourists, visitors, wanderers, refugees, and those returning home after a migration. The book is carefully divided into eight chapters, each dealing with a specific phase in sequential order. It begins with an overview