tbuckley/cabot-search huggingface dataset:
Proteasomal degradation of retinoid X receptor α reprograms transcriptional activity of PPARγ in obese mice and humans
Authors: Bruno Lefebvre, Yacir Benomar, Aurore Guédin, Audrey Langlois, Nathalie Hennuyer, Julie Dumont, Emmanuel Bouchaert, Catherine Dacquet, Luc Pénicaud, Louis Casteilla, Francois Pattou, Alain Ktorza, Bart Staels, Philippe Lefebvre
Journal: Journal of Clinical Investigation (2010)

Obese patients have chronic, low-grade inflammation that predisposes to type 2 diabetes and results, in part, from dysregulated visceral white adipose tissue (WAT) functions. The specific signaling pathways underlying WAT dysregulation, however, remain unclear. Here we report that the PPARgamma signaling pathway operates differently in the visceral WAT of lean and obese mice. PPARgamma in visceral, but not subcutaneous, WAT from obese mice displayed increased sensitivity to activation by its agonist rosiglitazone. This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice. Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT. Finally, PPARgamma-RXRbeta heterodimers, but not PPARgamma-RXRalpha complexes, were able to efficiently dismiss the transcriptional corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) upon agonist binding. Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation. Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.
Low incidence of adenocarcinoma and high-grade intraepithelial neoplasia in patients with Barrett’s esophagus: a prospective cohort study
Authors: J. Martinek, M. Benes, P. Brandtl, T. Hucl, M. Vasicek, L. Voska, V. Lanska, V. Nosek, J. Spicak
Journal: Endoscopy (2008)

See also: Commentaire de travail de J. Martinek et al., pp. 711Endoscopy 2008; 40(09): 967-967DOI: 10.1055/s-0032-1306864
Letter by Winnik et al Regarding Article, “Conversion of Cardiovascular Conference Abstracts to Publications”
Authors: Stephan Winnik, Thomas F. Lüscher, Christian M. Matter
Journal: Circulation (2013)

11, 2012, issue of Circulation on the conversion of cardiovascular conference abstracts into full-text publications.The authors used an automated algorithm to analyze the fate of all abstracts presented at the Scientific Sessions of the American Heart Association, the American College of Cardiology, and the European Society of Cardiology between 2006 and 2008.Interestingly, fewer than a third of all abstracts initially presented were eventually published in peerreviewed journals within 2 years of the conference; furthermore, publication rates slowed dramatically thereafter.We agree with the authors that efforts to understand these delays in publication and to facilitate the dissemination of scientific knowledge are needed to accelerate the transition of scientific discovery into clinical practice.However, we admit to being surprised about their statements that the completeness and speed of conversion from abstract to publication are unknown (Abstract), that no previous study has systematically assessed the scientific yield of medical conferences (Clinical Perspective), and that future studies should examine the association of reviewer ratings with later publication (Discussion).3][4] Using a manual assessment of 1002 randomly selected abstracts from that conference, we investigated the association between numerous study factors, including study design and topic, numbers of enrolled patients, academic affiliation, and author sex, and their likelihood of acceptance at conference level, later publication, and subsequent citation (as a measure of overall impact) during a 5-year follow-up period.We observed a marked disparity between the predictors of full-text publication and those predicting later citation, highlighting the importance of factors like prospective and randomized study designs as key markers of scientific impact.Of note, beyond those abstracts actually presented at the European Society of Cardiology Congress, our analyses also included those abstracts submitted but not accepted for presentation, thus allowing us to track the fate of both accepted and rejected studies.We were therefore able to investigate the association of reviewer ratings with acceptance at conference level, differentiated according to presentation format, later full-text publication, and subsequent citation.
Genetic and Environmental Contributions to Platelet Aggregation
Authors: Christopher J. O’Donnell, Martin G. Larson, DaLi Feng, Patrice A. Sutherland, Klaus Lindpaintner, Richard H. Myers, Ralph A. D’Agostino, Daniel Levy, Geoffrey H. Tofler
Journal: Circulation (2001)

Background —Platelet aggregation plays an important role in arterial thrombosis in coronary heart disease, stroke, and peripheral arterial disease. However, the contribution of genetic versus environmental influences on interindividual variation in platelet aggregability is poorly characterized. Methods and Results —We studied the heritability of platelet aggregation responses in 2413 participants in the Framingham Heart Study. The threshold concentrations of epinephrine and ADP required to produce biphasic platelet aggregation and collagen lag time were determined. Mixed-model linear regression was used to calculate correlation coefficients within sibships and within spouse pairs. Variance and covariance component methods were used to estimate the proportion of platelet aggregation attributable to measured covariates versus additive genetic effects. After accounting for environmental covariates, the adjusted sibling correlations for epinephrine, ADP, and collagen lag time were 0.24, 0.22, and 0.31, respectively ( P =0.0001 for each). In contrast, adjusted correlations for spouse-pairs were −0.01, 0.05, and −0.02, respectively (all P &gt;0.30). The estimated heritabilities were 0.48, 0.44, and 0.62, respectively. Measured covariates accounted for only 4% to 7% of the overall variance in platelet aggregation, and heritable factors accounted for 20% to 30%. The platelet glycoprotein IIIa Pl A2 polymorphism and the fibrinogen Hind III β-148 polymorphism contributed &lt;1% to the overall variance. Conclusions —In our large, population-based sample, heritable factors play a major role in determining platelet aggregation, and measured covariates play a lesser role. Future studies are warranted to identify the key genetic variants that regulate platelet function and to lay the groundwork for rational pharmacogenetic approaches.
Incidence of postoperative infections in patients undergoing coronary artery bypass grafting surgery receiving antimicrobial prophylaxis with original and generic cefuroxime
Authors: Ekaterini Mastoraki, Argyris Michalopoulos, Ioannis Kriaras, Ero Mouchtouri, Matthew Falagas, Dimitra Karatza, Stefanos Geroulanos
Journal: Journal of Infection (2007)
Effect of vitamin D supplementation and ultraviolet B exposure on serum 25-hydroxyvitamin D concentrations in healthy volunteers: a randomized, crossover clinical trial
Authors: Z. Lagunova, A.C. Porojnicu, L. Aksnes, M.F. Holick, V. Iani, Ø.S. Bruland, J. Moan
Journal: British Journal of Dermatology (2013)

Solar ultraviolet (UV) radiation during the summer and vitamin D supplementation are two major sources of vitamin D for humans at northern latitudes. However, little is known about the relative efficiency of these two vitamin D sources.The main goal was to compare the efficiency of high-dose oral vitamin D3 supplementation (2000 IU per day for 30 days) with a simulated summer UV exposure [10 sunbed sessions to a total dose of 23·8 standard erythema doses (SED)] to improve vitamin D status.Healthy volunteers were randomized into two groups: group 1 received vitamin D supplementation followed by 10 whole-body sunbed exposures; group 2 started with 10 sunbed exposures followed by vitamin D supplementation.The oral supplementation with vitamin D3 resulted in a mean (SEM) serum 25-hydroxyvitamin D [25(OH)D] increase of 25·3 (5·4) nmol L(-1) . A similar increase, 19·8 (5·4) nmol L(-1) , was observed after simulated summer UV exposure. At the end of the study, serum 25(OH)D concentrations were similar in both groups.Twice-weekly whole-body sunbed exposure to a dose of 4·8 SED is equal to 2000 IU daily of oral vitamin D supplementation for 30 days and enough to achieve and maintain serum 25(OH)D concentrations > 75 nmol L(-1) in ~55% of cases. Based on our calculations, this dose corresponds to a cumulative weekly whole-body exposure of 3·4 SED (~ 40 min around midday during the summer at the latitude of Oslo).
Abstract 803: Genomic sequencing of meningiomas reveals oncogenic SMO and AKT1 mutations.
Authors: Priscilla Brastianos, Peleg M. Horowitz, Sandro Santagata, Robert T. Jones, Aaron McKenna, Gad Getz, Keith Ligon, Paul Van Hummelen, Matt Ducar, Alina Raza, Ashwini Sunkavalli, Laura MacConaill, Anat Stemmer-Rachamimov, David N. Louis, William C. Hahn, Ian Dunn, Rameen Beroukhim
Journal: Cancer Research (2013)

Abstract Meningiomas are the most common primary brain tumor in the US. While many Grade I meningiomas are cured by surgery, 20% recur and are minimally responsive to systemic therapy. Meningiomas of higher grades are particularly challenging to treat and are associated with a poor prognosis. Though the tumor suppressor gene NF2 has been linked to meningiomagenesis, the spectrum of genetic changes in meningiomas remains poorly understood, particularly in the large subset of tumors without NF2 alterations. We performed whole-exome or whole-genome sequencing on 17 meningiomas and focused sequencing using a 645 gene-set on an additional 48 tumors. The majority of meningiomas exhibited simple genomes, with fewer copy-number alterations, mutations, and rearrangements compared to other adult tumors. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors. A subset of NF2-wildtype meningiomas harbored recurrent oncogenic mutations in AKT1 and the Hedgehog pathway regulator SMO. Tumors with these mutations varied histologically from their NF2-mutated counterparts, and exhibited immunohistochemical evidence of pathway activation. These results begin to define the spectrum of genetic alterations in meningiomas. Our findings of known driver oncogenic mutations including AKT1 and SMO have immediate therapeutic potential. Citation Format: Priscilla Brastianos, Peleg M. Horowitz, Sandro Santagata, Robert T. Jones, Aaron McKenna, Gad Getz, Keith Ligon, Paul Van Hummelen, Matt Ducar, Alina Raza, Ashwini Sunkavalli, Laura MacConaill, Anat Stemmer-Rachamimov, David N. Louis, William C. Hahn, Ian Dunn, Rameen Beroukhim. Genomic sequencing of meningiomas reveals oncogenic SMO and AKT1 mutations. [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 803. doi:10.1158/1538-7445.AM2013-803
Plasma 8-methoxypsoralen concentrations in photochemotherapy of psoriasis
Authors: I.H. STEVENSON, K.J.A. KENICER, B.E. JOHNSON, W. FRAIN-BELL
Journal: British Journal of Dermatology (1981)

Journal Article Plasma 8‐methoxypsoralen concentrations in photochemotherapy of psoriasis Get access I.H. STEVENSON, I.H. STEVENSON Departments of Pharmacology and Therapeutics, and Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar K.J.A. KENICER, K.J.A. KENICER Departments of Therapeutics and Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar B.E. JOHNSON, B.E. JOHNSON Departments of Therapeutics and Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar W. FRAIN‐BELL W. FRAIN‐BELL Departments of Therapeutics and Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 104, Issue 1, 1 January 1981, Pages 47–52, https://doi.org/10.1111/j.1365-2133.1981.tb01710.x Published: 01 January 1981 Article history Accepted: 24 April 1980 Published: 01 January 1981
Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy
Authors: V Dubois, F Sloan-Béna, A Cesbron, B G Hepkema, K Gagne, S Gimelli, D Heim, A Tichelli, J Delaunay, M Drouet, S Jendly, J Villard, J-M Tiercy
Journal: Leukemia (2012)
Effect of prior intragastric antigen administration on primary and secondary anti-ovalbumin responses of C57BL/6 and NZB mice.
Authors: J S Cowdery, M F Curtin, A D Steinberg
Journal: The Journal of Experimental Medicine (1982)

We evaluated the effect of antigen feeding on the subsequent primary and secondary anti-ovalbumin (OVA) responses of C57BL/6 and NZB mice. When C57BL/6 mice were given a single 20-mg dose of OVA intragastrically, profound tolerance was observed after challenge, 7 d later, with 125 micrograms of OVA in complete adjuvant or after two injections of 5 micrograms of OVA adsorbed to alum given 7 and 21 d after antigen feeding. OVA-fed NZB mice failed to become tolerant to a primary challenge with OVA in complete adjuvant, but showed a degree of tolerance similar to that of C57BL/6 mice when challenged two or three times with OVA in alum. These studies demonstrate that NZB mice fail to show tolerance at the level of the primary response after antigen feeding; however, they are normally tolerant when a secondary response to a lower dose of antigen is evaluated. This study suggests that, after antigen feeding, different mechanisms of tolerance may be involved in the regulation of primary and secondary responses.
China's health insurance system is failing poor people
Authors: Mary Hennock
Journal: BMJ (2007)

China's vigorous attempts to provide its vast population with better access to health care in the past few years have largely misfired, a World Health Organization study concludes.

Although overall spending on health care has risen by an average of 15% to 22% a year since the 1990s, much has been absorbed by the soaring costs of hospital care rather than being used to create the safety net of comprehensive care that was intended, said a WHO official.

What's more, new health insurance schemes for both city and country areas have failed to make medical treatment affordable for poor people, says the report.

China's government has made it a priority to improve access of its poorer citizens to medical treatment, under the …
Treatment Strategies for Prostate Cancer
Authors: Martin H. Cohen
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Discrimination abounds in our society. The latest victims appear to be men over the age of 60 years with biopsy-documented prostate cancer. The study by Fleming et al<sup>1</sup>and the accompanying Editorial by Whitmore<sup>2</sup>suggest that watchful waiting is appropriate therapy for many of these individuals. There are two problems with this approach. First, what are we waiting for? Are we waiting for symptomatic disease, for development of a palpable tumor mass, for a PSA level to increase 25%, 50%, 100%, or are we waiting for a new, nontoxic therapy? For some men, the wait will be too long. The second problem, more relevant to the discrimination issue, is that we are willing to give toxic chemotherapy to women with node-negative breast cancer who may have been "cured" by definitive local therapy. Randomized chemotherapy trials demonstrate that approximately 50% of women in the surgery-only control
Malignant Lymphomas Other Than Hodgkin's Disease: Histology, Cytology, Ultrastructure, Immunology
Authors: Richard L. Meyer
Journal: JAMA (1979)

This superbly organized, well-written text is divided into six main divisions. Part one is entitled "Cytological, Histological, and Functional Basis for a Modern Classification of Lymphomas." This section includes a description of the physiological condition of the various types of normal lymphocytes and correlates their function with their histomorphological condition. There are many excellent photomicrographs clarifying the author's word picture. The second division is a short chapter on the "Methodological Prerequisites for the Differential Diagnosis of Lymphomas." This is strictly for the pathologist, as it outlines various staining techniques to point out important differences in making a histological diagnosis as practiced in Dr Lennert's laboratory. Part three is "Classification of Non-Hodgkin's Lymphoma." This section and the next, "Histopathology and Diagnosis of Non-Hodgkin's Lymphoma," will be of most interest to the clinician. A short historical overview and comparisons of the various classifications are the main focus of the short chapter on
Tea and empathy
Authors: Paul McIntyre
Journal: BMJ (2005)

Ropivacaine, introduced in 1995, is an amide-type local anaesthetic.It consists of pure optical S-(-)-isomers and has a low cardiotoxicity.We report delayed hypersensitivity reactions to ropivacaine.A 74 year old man with postherpetic neuralgia started taking amitriptyline, alprazolam, and loxoprofen and underwent an epidural block with 0.2% ropivacaine hydrochloride without preservatives (48 ml or 96 ml daily).He had no history of allergy to any local anaesthetics.Two weeks later, purpuric rash appeared on his legs, and two days afterwards he developed a widespread blotchy erythema on his trunk and arms (figure).Laboratory examination showed normal white cell and platelet counts and slight eosinophilia (640/mm 3 ).The epidural block and the drugs were stopped, and the eruptions completely resolved within seven days.We did an intradermal test with 0.2% ropivacaine from a plastic ampoule without a rubber stopper.Erythema (maximum size was 23 mm×13 mm) appeared 8-72 hours after the injection.We did the test again and took a specimen for biopsy.Histology showed perivascular infiltrates of lymphocytes and eosinophils in the dermis.Patch testing with amitriptyline, alprazolam, and loxoprofen induced no eruptions, nor did restarting the drugs.Eleven cases of delayed-type hypersensitivity reactions have been reported, caused by local injections of amides such as lignocaine, mepivacaine, and prilocaine. 1-5The symptoms were erythema, papules, vesicles, and swelling, but they did not include purpuric rash.No cases related to an epidural block or ropivacaine have been reported.Ropivacaine may cause allergic reactions characterised by signs such as urticaria, angioneurotic oedema, tachycardia, and vomiting, but delayed hypersensitivity reactions are not referred to in the Physicians' Desk Reference.The manufacturer also has had no similar reports.
Radioactive Bullets Raise Cancer Fears
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Radioactive Bullets Raise Cancer Fears Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 13, 7 July 1993, Pages 1029–1030, https://doi.org/10.1093/jnci/85.13.1029 Published: 07 July 1993
Public health is good for you
Authors: S. Gibbs, N. Thalange
Journal: BMJ (1999)

We were, for a time, public health chaps. We stepped off the conveyor belt of our clinical training to spend time on the other side of the fence grappling with the broader determinants of health and disease and getting a feel for the medical arm of NHS management. We feel we are better people for having done it and would warmly recommend the experience to anyone interested in doing the same.

The Anglia public health training scheme offers two fellowships in public health and epidemiology every year. These fellowships allow specialist registrars from any specialty to spend six months or a year working in a department of public health medicine. The projects undertaken, and the skills and experience gained, can be tailored for the particular interests and needs of individuals but are likely to include some of the following broad areas: epidemiology and statistics; contracting, budgeting and prioritisation; guideline development; service review; audit, quality and clinical governance; health needs assessment; and the promotion of a knowledge based service.

This is a question that haunts even those within the confines of public health. One of the hallmarks of the specialty seems to be a constant search for self definition and clear objectives.

It is now known that public health is not just about drains but is, in fact, a little like a religion, a whole way of life.1 In essence it is the application of medical principles to populations rather than individuals. The practice of public health therefore involves not only promoting health and preventing disease (as if that were not enough) but also maximising the benefits of clinical services.Increasingly, the importance of coordinating the efforts …
GPs don't have "time or inclination" to make necessary changes to NHS, report says
Authors: N. Hawkes
Journal: BMJ (2013)

Clinical commissioning groups will need an unusual combination of skills to meet the challenges that the NHS in England faces, new research concludes.1 

And it is far from clear that GPs­­­—the chosen instruments for exercising clinical leadership under the reorganisation of the NHS—have either the time or the inclination to make it work.

John Storey and Richard Holti of the Open University studied the role of clinical leadership in the redesign of sexual health and dementia services in London and Manchester. They said that clinical leadership was often seen as the answer to the problem of managing rising demand without any more money, but they added that such declarations often underestimated the actual challenge and failed …
An Impacted Fracture of the Femoral Neck
Authors: Otto E. Aufranc
Journal: JAMA (1970)

Dr. Butler: The case for today is an impacted fracture of the femoral neck. It will be presented in several parts with discussion after each. A 43-year-old woman slipped and fell on the ice on Jan 1, 1969, landing on her left hip. She was helped to their car by her brother, and taken to a local emergency room for examination. X-ray films (Fig 1) revealed an impacted fracture of the left femoral neck. She had sustained no other injuries, and was in excellent general health. Dr. Aufranc will discuss the management of this case. Dr. Aufranc: The impacted fracture of the neck of the femur will always present the same dilemma, namely, is it favorably or unfavorably impacted? How can we tell without giving it a "test of labor"? Do we find, if it holds together, that it is favorably impacted? Or do we assume, if it falls apart,
Serum Lipoprotein Stability in Atherosclerosis
Authors: LOUIS HORLICK
Journal: Circulation (1954)

The alpha toxin of Clostridium welchii is a potent lecithinase which disrupts the serum lipoproteins, eventually resulting in complete separation of the lipids from the protein fraction. This reaction is associated with the development of turbidity, the intensity of which is related to the quantitative level of serum lipids. The time of onset of turbidity, however, appears to relate to the stability of the serum lipoprotein bond. Individuals with coronary disease showed early development of turbidity and high final turbidity in 64 per cent as compared with 14 per cent in a control group and 6 per cent in a group of young normal subjects.