tbuckley/cabot-search huggingface dataset:
Abstract 208: The MAGE family of cancer-testis antigens are potent oncogenes
Authors: P. Ryan Potts, Jennifer M. Doyle, Yi-Heng Hao, Elizabeth Kleinschmidt
Journal: Cancer Research (2012)

Abstract Introduction: Cancer-testis antigens (CTAs), including the MAGE protein family, are genes whose expression is typically restricted to the germline, but are aberrantly expressed and presented as antigens in human tumors. Therefore, CTAs constitute excellent targets for cancer immunotherapy. Surprising recent evidence suggests that the aberrant expression of MAGE CTAs in tumors is not simply an inert consequence of widespread genomic deregulation, but rather an important functional event promoting tumorigenesis. Furthermore, the expression of MAGE CTAs correlates with poor prognosis in a variety of cancer types. However, the role of MAGE CTAs as oncogenes driving tumorigenesis has been unexplored and their biochemical activity of MAGEs has been enigmatic. Aims and Methods: In this study, we investigated the function of the large MAGE protein family. First we determined the oncogenic potential of more than 20 MAGE CTAs in 3T3 transformation assays, soft agar anchorage-independent growth assays, and matrigel transwell invasion assays. We then selected several of these oncogenic MAGE CTAs for further in-depth study to identify their biochemical and cellular functions. Using a variety of in vitro and cellular assays, we identified common binding partners of more than ten MAGE proteins, solved the crystal structure of one MAGE protein, and investigated the biochemical activity of several MAGE CTAs. Results and Conclusions: We found that the majority of MAGE CTAs (more than 15) have oncogenic activity in cell transformation, anchorage-independent growth, and/or invasion. Additionally, we showed that a common feature of MAGE proteins is their ability to bind to and enhance the activity of E3 RING ubiquitin ligases, such TRIM28/KAP1, through a conserved tandem winged-helix domain. Importantly, we discovered that several MAGE-TRIM28 ubiquitin ligase complexes directly ubiquitylate and degrade the critical p53 tumor suppressor in vitro and in cancer cells. Thus, our findings clearly establish that MAGE CTAs function as oncogenes through their ability to regulate the activity of E3 RING ubiquitin ligases, resulting in the deregulation of vulnerable signaling pathways (such as the p53 tumor suppressor). These results underscore the importance of MAGE proteins as therapeutic targets for cancer and highlight a novel germline signaling program co-opted by cancer cells to facilitate tumorigenesis. 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 208. doi:1538-7445.AM2012-208
More than 15% of antibiotic sales in Greece are over the counter
Authors: R. Watson
Journal: BMJ (2010)

Fifteen European Union countries have national strategies in place on the prudent use of antimicrobials, a further eight are preparing them, and just four have no plans to do so, a new European Commission report says.

This is the second assessment of the extent to which the recommendation agreed by EU governments in 2001 on the prudent use of antimicrobials in humans is being put in place by the 27 member states and Norway (http://ec.europa.eu/health/antimicrobial\_resistance/docs/amr\_report2_en.pdf).

The initiative listed specific areas where action needed to be taken. These include the implementation of national strategies and action plans, …
Design, engineering and <i>in vitro</i> evaluation of MHC class‐II targeting allergy vaccines
Authors: R. Crameri, S. Flückiger, I. Daigle, T. Kündig, C. Rhyner
Journal: Allergy (2007)

Background: The worldwide increasing incidence of allergic diseases requires the development of new, efficient vaccination strategies, the only curative treatment with a long‐lasting effect. Current allergen‐specific immunotherapy protocols suffer from limited efficacy and a long treatment time. Methods: We engineered modular antigen translocating (MAT) molecules for intracellular targeting of allergens to the major histocompatibility class‐II (MHC‐II) presentation pathway to enhance antigen presentation. MAT‐fusions were evaluated for their ability to localize intracellularly, to induce proliferation, and for their influence on cytokine patterns in peripheral blood mononuclear cells (PBMCs) cultures. Results: We show that MAT‐allergen fusions are able to rapidly translocate into the cytoplasm of PBMCs, whereas naked recombinant allergens are only marginally taken up. MAT vaccines accumulate intracellularly and induce strong proliferation of PBMC cultures at concentrations 10–100 times lower than the corresponding naked allergens, indicating an enhanced presentation through the MHC‐II presentation pathway. In PBMC cultures of allergic donors, MAT vaccines induce a cytokine shift from a T H 2 to a T H 1 profile, resulting in a stronger and earlier secretion of INF‐ γ and Interleukin (IL)‐10, and a decreased secretion of IL‐4, IL‐5 and IL‐2, compared with those induced by the corresponding recombinant allergens. Conclusion: Modular antigen translocation vaccines induce strong proliferation responses in PBMC cultures at low concentration and induce a T H 1/T H 2 shift in the cytokine profile, reflecting those reported to occur in successfully desensitized allergic patients. Therefore, MAT molecules represent promising lead compounds for the development of potent allergy vaccines.
Role of magnesium in the failure of rhDNase therapy in patients with cystic fibrosis
Authors: N N Sanders, H Franckx, K De Boeck, J Haustraete, S C De Smedt, J Demeester
Journal: Thorax (2006)

<b>Background:</b> In the management of cystic fibrosis (CF), rhDNase-I inhalation is widely used to facilitate the removal of the highly viscous and elastic mucus (often called sputum) from the lungs. However, an important group of CF patients does not benefit from rhDNase-I treatment. A study was undertaken to elucidate the reason for the failure of rhDNase-I in these patients and to evaluate strategies to overcome this. <b>Methods:</b> The biochemical properties, physical properties, and degradation by rhDNase-I of sputum obtained from clinical responders and non-responders to rhDNase-I were compared, and the ability of magnesium to reactivate rhDNase-I in DNA solutions and in sputum was investigated. The effect of oral magnesium supplements on magnesium levels in the sputum of patients with CF was also examined. <b>Results:</b> Sputum from clinical responders was extensively degraded in vitro on incubation with rhDNase-I, while sputum from clinical non-responders was not degraded: the median decrease in sputum elasticity in the two groups was 32% and 5%, respectively. Sputum from clinical responders contained significantly higher concentrations of magnesium than sputum from non-responders (2.0 mM <i>v</i> 1.3 mM; p = 0.020). Sputum that could not be degraded by rhDNase-I became degradable after preincubation with magnesium. The effect of magnesium on rhDNase-I activity was mediated through actin. Oral intake of magnesium enhanced the magnesium concentration in the sputum of CF patients. <b>Conclusion:</b> Increasing the magnesium concentration in sputum by, for example, oral magnesium supplements may be a promising new strategy to overcome the failure of rhDNase-I in patients with CF.
Does oxygen help dyspnea in patients with cancer?
Authors: S Booth, M J Kelly, N P Cox, L Adams, A Guz
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Dyspnea in patients with advanced cancer is a common symptom that is difficult to treat. This study investigated whether oxygen helps to relieve rest dyspnea in patients with advanced cancer. In a single-blind controlled trial, oxygen and air were administered in random order to hospice patients reporting dyspnea at rest. Measurements of arterial oxygen saturation, lung function, and dyspnea (using a visual analogue scale [VAS] and Borg score) were made before and after each gas had been given for 15 min. Data from 38 patients were used: analysis of variance revealed that mean VAS levels during baseline conditions, breathing room air (59 mm), were significantly reduced after administration of either air (48 mm; p < 0.001) or oxygen (45 mm; p < 0.001); there was no significant difference for the mean VAS scores between oxygen and air administration. There was no statistically significant order of treatment effect. There was no difference in the response to oxygen or air in patients with a history of cardiopulmonary disease. The improvement in dyspnea with oxygen could not be predicted from a subject's initial level of hypoxia. Results suggested that benzodiazepines may potentiate the effect of oxygen. The overall conclusion is that oxygen and air can have a significant effect in reducing dyspnea at rest in patients with advanced cancer.
Queen's speech heralds health bills in Britain
Authors: J. Warden
Journal: BMJ (1994)

New powers for the General Medical Council to discipline doctors whose performance is seriously deficient are included in the legislative programme of the British parliament for the 1994-5 session, which opened last week (see also Focus on p1394). A bill extending the Medical Act was one of three health measures in the Queen's speech. Of the others, one will streamline the administration of the NHS in England and a second will introduce supervised discharge for mentally ill patients. Though it is the heaviest agenda of health legislation for some years, all the bills seek to amend existing provisions rather than to innovate.

The bill to enable the General Medical Council to …
Book: Drug War Heresies: Learning from Other Vices, Times, and Places
Authors: M. Farrell
Journal: BMJ (2002)

Robert J MacCoun, Peter Reuter Cambridge University Press, £18.95, pp 496 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Every week seems to bring a new report on the failure of current drug policy. Rising levels of serious drug problems put new pressures on old systems that can barely cope anyway. Schools, psychiatric hospitals, and prisons continue to face fresh challenges. People from most walks of life have a view on drug policy and legalisation. The views are not easily cast along old left and right wing political lines. Europeans generally think that European drug policy has been more pragmatic and sensible that of the United States. Robert MacCoun and Peter Reuter are … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Gut microbiome, obesity, and metabolic dysfunction
Authors: Herbert Tilg, Arthur Kaser
Journal: Journal of Clinical Investigation (2011)

The prevalence of obesity and related disorders such as metabolic syndrome has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. As most findings in this field of research are based on mouse studies, the relevance to human biology requires further investigation.
Elevated Serum Levels of Soluble Tac Peptide in Adult T-Cell Leukemia: Correlation with Clinical Status during Chemotherapy
Authors: Luisa Marcon
Journal: Annals of Internal Medicine (1988)

Adult T-cell leukemia associated with human T-cell leukemia virus type I (HTLV-I) is characterized by a clonal expansion of a CD4-positive subset of T lymphocytes that constitutively express high numbers of interleukin-2 receptors and that frequently infiltrate the skin; osteolytic bone lesions; and hypercalcemia. Using an enzyme-linked immunosorbent assay (ELISA) test, we measured the level of soluble Tac peptide, one chain of the human interleukin-2 receptor, in the serum of 50 patients with adult T-cell leukemia (38 Japanese and 12 American patients), 8 patients with other hematologic malignancies, 8 asymptomatic HTLV-I-antibody-positive carriers, and 17 normal controls. The serum level of soluble Tac peptide (geometric mean U/mL, 95% CI) was elevated at presentation in all patients with adult T-cell leukemia (16 461; 819 to 330 896) when compared with normal controls (238; 112 to 502), patients with other hematologic malignancies (1302; 475 to 3569), and healthy HTLV-I antibody-positive carriers (490; 115 to 2086). The highest levels were seen in patients (n = 33) with acute (32 154; 2587 to 399 598) compared with chronic (5464; 661 to 45 156) disease (n = 14). Serum levels of Tac peptide also tended to be more elevated in patients with adult T-cell leukemia with hypercalcemia (32 072; 2461 to 417 908) compared with normocalcemic patients (13 885; 496 to 388 436). Serial measurements of soluble Tac peptide levels in serum were done in four patients with adult T-cell leukemia during chemotherapy and the levels reflected disease activity. These observations suggest that the measurement of soluble Tac peptide levels in patients with adult T-cell leukemia is useful as a noninvasive measure of tumor burden and will help in the diagnosis of the disease and management of these patients.
Evaluation of drug phototoxicity by photosensitization of <i>Trichophyton mentagrophytes</i>
Authors: TAKESHI HORIO
Journal: British Journal of Dermatology (1981)

SUMMARY Long wave ultraviolet radiation to suspensions of T. mentagrophytes, in the presence of photosensi tizing chemicals, resulted in death of the fungus as measured by loss in colony-forming ability. Photosensitization could be demonstrated, with appropriate exposures and concentrations, with chlorpromazine, promethazine, perphenazine, anthracene, sulphanilamide, trimethylpsoralen, tolbutamide, tetrachlorosalicylanilide, and tribromosalicylanilide. No phorotoxicity was detected with demethylchlortetracycline and thiazides. The present system seems to be simple, reproducible, and sensitive as an in vitro screening test for the photosensitizing potential of chemicals.
DOUBLE-BLIND RANDOMISED TRIAL OF ORG 10172 LOW-MOLECULAR-WEIGHT HEPARINOID IN PREVENTION OF DEEP-VEIN THROMBOSIS IN THROMBOTIC STROKE
Authors: AlexanderG.G Turpie, Jack Hirsh, RichardM Jay, Maureen Andrew, RussellD Hull, MarkN Levine, CedricJ Carter, PeterJ Powers, HarryN Magnani, Michael Gent
Journal: The Lancet (1987)
Assessment of Pharmacodynamic Vascular Response in a Phase I Trial of Combretastatin A4 Phosphate
Authors: Helen L. Anderson, Jeffrey T. Yap, Mathew P. Miller, Adele Robbins, Terry Jones, Patricia M. Price
Journal: Journal of Clinical Oncology (2003)

Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points that measure vascular damage. Positron emission tomography (PET) was used to measure the effects of the vascular targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue perfusion and blood volume.Patients with advanced solid tumors were enrolled onto part of a phase I, accelerated-titration, dose-escalation study. The effects of 5 to 114 mg/m2 CA4P on tumor, spleen, and kidney were investigated. Tissue perfusion was measured using oxygen-15 (15O)-labeled water and blood volume was measured using 15O-labeled carbon monoxide (C15O). Scans were performed immediately before, and 30 minutes and 24 hours after the first infusion of each dose level of CA4P. All statistical tests were two sided.PET data were obtained for 13 patients with intrapatient dose escalation. Significant dose-dependent reductions were seen in tumor perfusion 30 minutes after CA4P administration (mean change, -49% at >or= 52 mg/m2; P =.0010). Significant reductions were also seen in tumor blood volume (mean change, -15% at >or= 52 mg/m2; P =.0070). Although by 24 hours there was tumor vascular recovery, for doses >or= 52 mg/m2 the reduction in perfusion remained significant (P =.013). Thirty minutes after CA4P administration borderline significant changes were seen in spleen perfusion (mean change, -35%; P =.018), spleen blood volume (mean change, -18%; P =.022), kidney perfusion (mean change, -6%; P =.026), and kidney blood volume (mean change, -6%; P =.014). No significant changes were seen at 24 hours in spleen or kidney.CA4P produces rapid changes in the vasculature of human tumors that can be assessed using PET measurements of tumor perfusion.
Pathological Contributions to Medical Jurisprudce
Authors: W. B. Mushet
Journal: BMJ (1859)

A few doses of quinine, with or without steel, will act almost magically.Rest and good diet should be added, if possible.Several instances, where tle quasi-lheroic plasters and lini- ments of croton oil and tartarised antimony (tlhough, be it understood, from no want of apparent potency) have failed to relieve the latient, I have fouind to yield at once to the above named remedies.Internal antirheumatic alkaline or depressing agents do not, so far as I have tried them, exert any favourable ijufluence whatever.The characters of the urine might almost be spoken of as dia,nostic in each instance.Repeated examinations of urine -from patients of each class have made me believe that their respective characters are very iairly constant; and that from this circumstance alone, the appropriate treatment miight be deduced.I do not thiniik that the distinction of the two classes with the widely (lilerent treatment ;s sufficiently recognised or acted on.Poor as this modicum of contribution is, I yet believe that it has some trace of corr-ectniess for its basis; and II shall be initerested to know how far those meembers of the Associationi, wlho have worked out muscular affections much more thoroughly, are inclined to agree with the division suggested.
Case of Retention of Menstrual Fluid in the Fallopian Tube: a Reply to Dr. Harley
Authors: L. Tait
Journal: BMJ (1878)

September 28th, I872, mentions a number of diseases which arise from water so contaminated.Among others, he names gottre, cretification of the arteries and valves of the heart, rheumatic arthritis, and calcareous deposits in various organs.In this district, anaemia is soon produced, wlien young females, especially from the South of England, come to reside here.This is a most frequent occurrence among the domestic servants of the neighbourhood.The majority of the young girls, living in the small farm-houses scattered over the moors and in the sequestered valleys, are highly anaemic in appearance, and are often under treatment for that condition.Pregnancy has a powerful effect on goitre.Many bronchoceles ap- pear during the first pregnancy, or are noticed immediately after the first labour; the popular notion being that the swelling is due to the exertion of bearing down during the-expulsion of the child in delivery.
Dentin matrix protein 1 induces membrane expression of VE-cadherin on endothelial cells and inhibits VEGF-induced angiogenesis by blocking VEGFR-2 phosphorylation
Authors: Sophie Pirotte, Virginie Lamour, Vincent Lambert, Maria-Luz Alvarez Gonzalez, Sandra Ormenese, Agnès Noël, Denis Mottet, Vincent Castronovo, Akeila Bellahcène
Journal: Blood (2010)
After-Dinner Speaking — Hello, There!
Authors: John Lister
Journal: New England Journal of Medicine (1968)

THE lone lay guest at a medical dinner is often at a disadvantage when he has been well wined and dined and then finds that he has been summoned to his feet to "sing for his supper." If, however, he happens to be a lawyer he can be counted upon to sing well, and the doctors can usually be sure of good postprandial entertainment. This was the case on a recent occasion when a local medical society had an eminent judge as its guest.Predictably, he began by saying that he knew that many doctors complained of being kept waiting . . .
NON-ACCESS SITE BLEEDING AFTER TRANSRADIAL OR FEMORAL PROCEDURES IN LONG TERM WARFARIN PATIENTS
Authors: Zohair Raza, Maryam Mohammadi, Gautam Visweswaran, Abdul Waheed, S. Sadi Raza, Chuntao Wu, Ian Gilchrist
Journal: Journal of the American College of Cardiology (2012)
Boston Nutrition Society, Inc., Plaintiff vs Fredrick J. Stare, Defendant
Authors: Fredrick J. Stare
Journal: JAMA (1963)

THE DEFENDANT maliciously, intending to defame the plaintiff and subject it to hatred, ridicule and contempt,... falsely, maliciously, willfully, wrongfully... published... a fake, wicked, malicious, defamatory and scandalous libel...." These harsh words with their interesting adjectives, originated by the Boston Nutrition Society, were delivered to me the first Monday in July, 1959. The basis for this libel suit was an answer I had prepared to a question received from the editorial staff of<i>McCall's</i>magazine, and which was to appear in the March, 1957, issue as part of a question and answer column. The complete question and my answer were as follows: "Q. I am enclosing a clipping from an 'open letter' from the Boston Nutrition Society that is really frightening: 'The enriched white bread fed to the American public is a national scandal. First of all, the wheat grown on poor soil and fertilized with water-soluble commercial fertilizer
Doctors who default on loans shamed on the internet
Authors: D. Josefson
Journal: BMJ (1998)

Doctors and other health professionals in the United States who have not repaid their student loans have had their names publicised on the internet and are to be disqualified for payment by the Medicare and Medicaid programmes, the Department of Health and Human Services has announced.

The move is a radical attempt to recover over $107m (£67m) owed …
567 The in-vitro effect of terfenadine on neutrophil chemotactic activity (NCA) and eosinophil chemotactic activity (ECA) after inhalation of platelet activating factor (PAF)
Authors: C OKADA, H MIYAGAWA, H SUGIYAMA, R EDA, R HOPP, A BEWTRA, R TOWNLEY
Journal: Journal of Allergy and Clinical Immunology (1991)
Two Welsh surveys of blood lead and blood pressure.
Authors: P C Elwood, G Davey-Smith, P D Oldham, C Toothill
Journal: Environmental Health Perspectives (1988)

The relationship between blood pressure and blood lead was examined in two population samples. One of these consisted of 1137 men aged 49 to 65 years, the other of 865 men and 856 women aged 18 to 64 years. Neither population had any known important exposure to lead, and the 95% ranges of blood lead levels were 6 to 26 micrograms/100 mL and 6 to 23 micrograms/mL in the men and 5 to 18 micrograms/100 mL in the women. No significant relationship between blood pressure and blood lead was detected in either of the population samples, and the regression coefficients suggest that if there were a real effect, then the mean difference in blood pressure per 10 micrograms difference in blood lead is likely to be 0.7 mm Hg in both systolic and diastolic pressures. In the survey of 1137 men, the rise in blood pressure was measured during the cold pressor test. This test is likely to be affected if lead were to affect neurogenic mediators of blood pressure. The mean change in systolic pressure was 24 mm Hg and the 95% range was -6 to 60 mm Hg, but there was no evidence of any association with blood lead level.
Comparison Between Methacholine And Mannitol Tests For The Study Of Bronchial Hyperresponsiveness In Asthma Induced By Exercise In Pediatric Athletes
Authors: M. Andregnette, M. Fernandez Nieto, L. Arochena, M. Garcia Del Potro, E. Aguado, J. Sastre
Journal: Journal of Allergy and Clinical Immunology (2012)