tbuckley/cabot-search huggingface dataset:
Abstract 4891: Radiation enhances the efficacy of Bcl-2 and Bcl-XL inhibition in small cell lung cancer: A new concept of using radiation for targeted therapy through contextual oncogene addiction
Authors: Yohann Loriot, Pierre Mordant, Delphine Dugué, Andrea Gombos, Paule Opolon, Marie-Catherine Vozenin, Jean Bourhis, Olivier Geneste, Laurence Kraus-Berthier, Alain Pierré, Stéphane Depil, Jean-Charles Soria, Eric Deutsch
Journal: Cancer Research (2012)

Abstract Purpose: Radiotherapy has a critical role in the treatment of small cell lung cancer (SCLC). Effectiveness of radiation in SCLC remains limited as resistance results from defects in apoptosis. Experimental Design: We investigated whether using a new Bcl-2/Bcl-XL inhibitor, S44563, can enhance radiosensitivity of SCLC cells in vitro and in vivo. We also explored the mechanisms of the potential interaction. Results: In vitro studies confirmed that S44563 induce apoptosis in SCLC cells by inducing hallmarks of apoptosis (cleaved caspase-3, sub-G1 fraction induction and induction of the mitochondrial caspase activation pathway). S44563 markedly enhanced sensitivity of H146 and H69 cells to radiation in clonogenic assay. In vitro experiments demonstrated a greater induction of apoptosis (sub-G1 fraction and cleaved caspase-3) with the combination as well as in vivo caspase-3 immunostaining. This positive interaction between S44563 and radiation was greater when S44563 was given during and after the completion of the radiation, which was explained by the radiation-induced over expression of anti-apoptotic proteins (Bcl-2 and Bcl-XL). in vitro studies based on gene expression and immunoblotting indicated that radiation activates NF-κB pathways which results in anti-apoptotic expression. In addition, S44563 combined with cisplatin-based chemo-radiation showed a dramatic tumor growth delay and increased overall survival in mouse xenograft models.Conclusion: This study underlines the critical role of sequence administration of targeted therapies with conventional therapies such as radiation and chemotherapy. SCLC cells which survive to IR highly rely on the induction of anti apoptotic proteins for their survival therefore yielding to the concept of “contextual oncogene addiction” to the Bcl-2/Bcl-XL pathway. These results suggest that radioresistance results in part from resistance to apoptosis in SCLC mediated by up regulation of Bcl-2/Bcl-XL. The inhibition of Bcl-2 and Bcl-XL leads to the induction of radiation-induced apoptosis and enhances radiation therapy both in vitro and in SCLC xenograft models. Our data suggest that targeting radiation induced survival pathways may constitute an efficient strategy to potentiate IR. 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 4891. doi:1538-7445.AM2012-4891
A Lifelong Study — Musical Therapy —<i>Rock around the Clock</i>
Authors: John Lister
Journal: New England Journal of Medicine (1956)

THE first World Conference on Medical Education gave an unprecedented stimulus to thought on the problem of how to turn out properly trained doctors. At the beginning of each new academic year, there are new thoughts on this old theme. As the mass of detailed scientific knowledge increases and the tendency toward ever-narrower specialization becomes more marked, so it becomes more apparent each year that the student must be taught to think and not to try to remember an increasing number of facts.Professor Pickering, the recently appointed Regius Professor of Medicine at Oxford, believes that the problem lies in . . .
Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein in the cell lines of the National Cancer Institute Anticancer Drug Screen.
Authors: M Alvarez, K Paull, A Monks, C Hose, J S Lee, J Weinstein, M Grever, S Bates, T Fojo
Journal: Journal of Clinical Investigation (1995)

Identifying new chemotherapeutic agents and characterizing mechanisms of resistance may improve cancer treatment. The Anticancer Drug Screen of the National Cancer Institute uses 60 cell lines to identify new agents. Expression of mdr-1/P-glycoprotein was measured by quantitative PCR. Expression was detected in 39 cell lines; the highest levels were in renal and colon carcinomas. Expression was also detected in all melanomas and central nervous system tumors, but in only one ovarian carcinoma and one leukemia cell line. Using a modified version of the COMPARE program, a high correlation was found between expression of mdr-1 and cellular resistance to a large number of compounds. Evidence that these compounds are P-glycoprotein substrates includes: (a) enhancement of cytotoxicity by verapamil; (b) demonstration of cross-resistance in a multidrug-resistant cell line, (c) ability to antagonize P-glycoprotein, increasing vinblastine accumulation by decreasing efflux; and (d) inhibition of photoaffinity labeling by azidopine. Identification of many heretofore unrecognized compounds as substrates indicates that P-glycoprotein has a broader substrate specificity than previously recognized. This study confirms the validity of this novel approach and provides the basis for similar studies examining a diverse group of gene products, including other resistance mechanisms, putative drug targets, and genes involved in the cell cycle and apoptosis.
Effect of ketone infusions on amino acid and nitrogen metabolism in man.
Authors: R S Sherwin, R G Hendler, P Felig
Journal: Journal of Clinical Investigation (1975)

To evaluate the role of hyperketonemia in the hypoalaninemia and decreased protein catabolism of prolonged starvation, Na dl-beta-hydroxybutyrate was administered as a primed continuous 3-6-h infusion in nonobese subjects and in obese subjects in the postabsorptive state and after 3 days and 3-5 1/2 wk of starvation. An additional obese group received 12-h ketone infusions on 2 consecutive days after 5-10 wk of fasting. The ketone infusion in nonobese and obese subjects studied in the postabsorptive state resulted in total blood ketone acid levels of 1.1-1.2 mM, a 5-15 mg/100 ml decrease in plasma glucose, and unchanged levels of insulin, glucagon, lactate, and pyruvate. Plasma alanine fell by 21% (P smaller than 0.001) in 3 h. In contrast, other amino acids were stable or varied by less than 10%. Infusions lasting 6 h reduced plasma alanine by 37%, reaching levels comparable to those observed in prolonged starvation. Equimolar infusions of NaC1 and/or administration of NaHCO3 failed to alter plasma alanine levels. During prolonged fasting, plasma alanine, which had fallen by 40% below prefast levels, fell an additional 30% in response to the ketone infusion. In association with repeated prolonged (12 h) infusions in subjects fasted 5-10 wk, urinary nitrogen excretion fell by 30%, returning to base line after cessation of theinfusions and paralleling the changes in plasma alanine. Ketone infusins resulted in two- to fourfold greater increments in blood ketone acids in fasted as compared to postabsorptive subjects. It is concluded that increased blood ketone acid levels induced by infusions of Na DL-beta-hydroxybutyrate result in hypoalaninemia and in nitrogen conservation in starvation. These data suggest that hyperketonemia may be a contributory factor in the decreased availability or circulating alanine and reduction in protein catabolism characteristic of prolonged fastings9
CINE BALANCED STEADY-STATE FREE PRECESSION IS A RELIABLE ALTERNATIVE TO CONVENTIONAL T2-WEIGHTED IMAGING AND EVANS BLUE FOR THE CMR ASSESSMENT OF AREA AT RISK AFTER MYOCARDIAL INFARCTION
Authors: Carlos G. Santos-Gallego, Torsten Vahl, Georg Goliasch, Kiyotake Ishikawa, Roger J. Hajjar, Valentin Fuster, Javier Sanz, Juan Jose Badimon
Journal: Journal of the American College of Cardiology (2013)
Preventing suicides must remain a priority
Authors: L. Appleby
Journal: BMJ (2001)

EDITOR—Davies et al are sceptical about the intention to reduce suicide set out in the national service framework on mental health, mainly because they regard suicide as rare.1 In fact, there are around 5000 suicides a year in England. This is more than the number of deaths in motor vehicle crashes and more than 10 times the number of deaths from …
Penetration of albendazole sulphoxide into hydatid cysts.
Authors: D L Morris, J B Chinnery, G Georgiou, G Stamatakis, B Golematis
Journal: Gut (1987)

The penetration of albendazole sulphoxide, the principal metabolite of albendazole into hydatid cysts (E granulosus) was measured by means of in vitro animal and clinical studies. The drug freely diffuses across the parasitic membranes. Cyst/serum concentrations of 22% were achieved in patients, longer pre-operative therapy produced higher concentrations.
MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial
Authors: Hong-Hu Zhu, Xiao-Hui Zhang, Ya-Zhen Qin, Dai-Hong Liu, Hao Jiang, Huan Chen, Qian Jiang, Lan-Ping Xu, Jin Lu, Wei Han, Li Bao, Yu Wang, Yu-Hong Chen, Jing-Zhi Wang, Feng-Rong Wang, Yue-Yun Lai, Jun-Yue Chai, Li-Ru Wang, Yan-Rong Liu, Kai-Yan Liu, Bin Jiang, Xiao-Jun Huang
Journal: Blood (2013)
Risk of Post-Transfusion Infection with the Hepatitis Delta Virus
Authors: Floriano Rosina, Giorgio Saracco, Mario Rizzetto
Journal: New England Journal of Medicine (1985)

Hepatitis delta virus is a defective virus that can replicate only in the presence of hepatitis B virus. To determine the prevalence, circumstances of transmission, and clinical importance of infection with hepatitis delta virus, we obtained data on 262 patients with post-transfusion hepatitis who were positive for the hepatitis B surface antigen (HBsAg) even though they had received blood screened for it. We also studied 94 HBsAg carriers who were receiving repeated blood transfusions for other diseases, and 103 HBsAg carriers with hemophilia who were receiving various forms of coagulation factors. Antibody to hepatitis delta virus was found in 9 of 262 patients (3.5 per cent) with post-transfusion hepatitis, 5 of 234 (2 per cent) with self-limited disease, and 4 of 28 (14.5 per cent) with fulminant disease (P less than 0.05). The absence of IgM antibodies to the hepatitis B core antigen indicated that three of the nine patients with both HBsAg and antibodies to hepatitis delta virus had been carriers of HBsAg at the time of transfusion, and the acute disease represented the combined effects of the two viruses. Antibody to hepatitis delta virus was found in 3 of 94 Italian carriers of HBsAg who were receiving repeated blood transfusions, in none of 24 Brazilian, East German, or Australian hemophiliac carriers infused with clotting factors prepared from single or mini-pool volunteer plasma, and in 27 to 100 per cent of 79 hemophiliac carriers from European and U.S. series who received coagulation factors manufactured from large pools of plasma. We conclude that infection with hepatitis delta virus is likely to be more severe than infection with hepatitis B virus alone and that screening for HBsAg provides a high degree of safety in preventing infection with hepatitis delta virus, but that the risk is considerably greater in patients who are already carriers of HBsAg. We recommend that HBsAg carriers be given only blood derivatives prepared from a single donor or mini-pool donors.
Cost-effectiveness of Mammography Screening-Reply
Authors: C. John Rosenquist
Journal: JAMA (1996)

In Reply.  —We appreciate the opportunity to respond to the provocative comments resulting from publication of our article.  Drs Donnelly and Lo are concerned because elements of disutility (anxiety, fear, and the like) were not included in the model. These disutilities are often not analyzed because of the difficulty in assigning values. Positive utilities were also ignored, including knowledge that cancer is not present and establishment of better health habits.  Drs Black and Tosteson suggest that we should analyze marginal cost-effectiveness of adding screening of the 40- to 49-year-old age group; this was the subject of a previous article. 1 They are correct that the cost-effectiveness of screening in the 40- to 49-year-old age group is highly sensitive to the assumed reduction in mortality. This is illustrated in Table 7 of our article and in the previous study. 1   We have the following responses to the five concerns about our
Tracking brain functions in space and time
Authors: Riitta Hari
Journal: Behavioral and Brain Sciences (1995)

Abstract The authors of Images of mind have been highly successful in unravelling the neural basis of complex brain functions. Their emphasis on top-down processingin experimental neuroscience is especially important and, it is hoped, influential. Tracking brain activation accurately botli in space and in time would benefit from studiesofindividual subjects without relying on grand average data.
<i>Paired box gene 5</i>is a novel tumor suppressor in hepatocellular carcinoma through interaction with p53 signaling pathway
Authors: Weili Liu, Xiaoxing Li, Eagle S.H. Chu, Minnie Y.Y. Go, Lixia Xu, Guijun Zhao, Lili Li, Ning Dai, Jianmin Si, Qian Tao, Joseph J.Y. Sung, Jun Yu
Journal: Hepatology (2010)

Abstract The paired box 5 ( PAX5 ) is a member of PAX transcription factors family involved in the regulation of embryonic development. However, the role of PAX5 in carcinogenesis is largely unclear. We identified that PAX5 is involved in human cancer by methylation-sensitive representational difference analysis. We examined the biological functions and related molecular mechanisms of PAX5 in hepatocellular carcinoma (HCC). Promoter methylation of PAX5 was evaluated by methylation-specific polymerase chain reaction (PCR) and bisulfite genomic sequencing (BGS). The functions of ectopic PAX5 expression were determined by viability assay, colony formation, and cell cycle analyses, along with in vivo tumorigenicity assays. The PAX5 target signal pathway was identified by promoter luciferase assay, chromosome immunoprecipitation (ChIP), and pathway PCR array. PAX5 is expressed in normal human liver tissue, but silenced or down-regulated in 83% (10/12) of HCC cell lines. The mean expression level of PAX5 was significantly lower in primary HCCs as compared to their adjacent normal tissues ( P &lt; 0.0001). The promoter methylation contributes to the inactivation of PAX5 . Restoring PAX5 expression in silenced HCC cell lines suppressed cell proliferation, induced apoptosis in vitro , and inhibited tumor growth in nude mice ( P &lt; 0.0001). The pathway luciferase reporter assay indicated that PAX5 activated p53 and p21 signaling. ChIP analysis demonstrated that PAX5 directly bound to the p53 promoter. The antitumorigenic function of PAX5 was at least up-regulated by p53 and its downstream targets including tumor necrosis factor, Fas ligand, leucine-rich repeats, and death domain-containing, poly(rC) binding protein 4, p21, and growth arrest and DNA-damage-inducible alpha. Conclusion: PAX5 is frequently inactivated by promoter methylation in HCC. PAX5 appears to be a functional tumor suppressor involved in liver carcinogenesis through direct regulation of the p53 signaling pathway. (Hepatology 2011)
Effect of epinephrine on cerebral and myocardial perfusion in an infant animal preparation of cardiopulmonary resuscitation.
Authors: C L Schleien, J M Dean, R C Koehler, J R Michael, T Chantarojanasiri, R Traystman, M C Rogers
Journal: Circulation (1986)

We assessed the efficacy of conventional cardiopulmonary resuscitation (CPR) in 2-week-old piglets. We determined intrathoracic vascular pressures, cerebral (CBF) and myocardial blood flows (MBF), and cerebral oxygen uptake during conventional CPR in this infant animal preparation and contrasted these results with those of previous work on adult animals. We further examined the effects of the infusion of epinephrine on these pressures and flows and on cerebral oxygen uptake, which has not been previously evaluated in adult preparations. Conventional CPR was performed on pentobarbital-anesthetized piglets with a 20% sternal displacement with the use of a pneumatic piston compressor. Chest recoil was incomplete, leading to an 18% to 27% reduction in anteroposterior diameter during the relaxation phase. Aortic and right atrial pressures in excess of 80 mm Hg were generated. These pressures are greater than those generally obtained in adult animals with similar percent pulsatile displacements. CBF and MBF were also initially greater than those reported in adult animals undergoing conventional CPR. However, when CPR was prolonged beyond 20 min, aortic pressure fell and CBF and MBF declined to the near-zero levels seen in adult preparations. At 5 min of CPR, CBF and MBF were 24 +/- 7 and 27 +/- 7 ml . min-1 x 100 g-1 (50% and 17% of the values during cardiac arrest), respectively. With the continuous infusion of epinephrine (4 micrograms/kg/min) in another group of animals, MBF was significantly greater at 20 min of CPR and CBF and cerebral O2 uptake were greater at 35 min of CPR as a result of higher perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal cell cancer and exposure to gasoline: a review.
Authors: J K McLaughlin
Journal: Environmental Health Perspectives (1993)

A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factors are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure.
ORIGIN OF ANTI-HUMAN BLOOD GROUP B AGGLUTININS IN WHITE LEGHORN CHICKS
Authors: Georg F. Springer, Richard E. Horton, Martin Forbes
Journal: The Journal of Experimental Medicine (1959)

While anti-human blood group B agglutinins are present in the majority of ordinary White Leghorn chicks by the age of 30 days, none could be demonstrated in germfree chicks up to the age of 60 days. Anti-B agglutinins in trace amounts were first found in germfree chicks 66 days old and increased to an average titer of about 1:2 by 91 days of age. This titer amounts to about 10 per cent of that found in ordinary chicks. The appearance of antibody in low titer is attributed to trace amounts of non-living antigenic contaminants penetrating the germfree barrier. The necessity of appropriate absorption in order to obtain well defined specificities was pointed out. Several means commonly used to differentiate between normal and immune antibodies were employed in this investigation. None showed a difference between anti-B agglutinins from ordinary chicks and from germfree chicks intentionally immunized with blood group B active E. coli O(86) or with B active preparations from human meconium. The implications of these findings on the origin of natural agglutinins are discussed. It is concluded, that measurable anti-human blood group B agglutinins in White Leghorn chicks are acquired early in life and are not inherited. The possibilities as well as limitations of present day germfree technique for this kind of immunological research have been considered.
1154-86 Hyperglycaemia reduces myocardial reperfusion during primary percutaneous coronary intervention for ST-elevation myocardial infarction
Authors: Jorik Timmer, Jan Paul Ottervanger, Amoud W.J van 't Hof, Jan C.A Hoorntje, Menko-Jan de Boer, Harry Suryapranata, Felix Zijlstra
Journal: Journal of the American College of Cardiology (2004)
Vulval adenosis associated with toxic epidermal necrolysis
Authors: J-C. Noel, F. Buxant, I. Fayt, G. Debusschere, D. Parent
Journal: British Journal of Dermatology (2005)

Journal Article Vulval adenosis associated with toxic epidermal necrolysis Get access J‐C. Noël, J‐C. Noël Departments of Dermatopathology and Gynecopathology, Erasme University Hospital, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium E‐mail: jenoel@ulb.ac.be Search for other works by this author on: Oxford Academic Google Scholar F. Buxant, F. Buxant Departments of Dermatopathology and Gynecopathology, Erasme University Hospital, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium E‐mail: jenoel@ulb.ac.be Search for other works by this author on: Oxford Academic Google Scholar I. Fayt, I. Fayt Departments of Dermatopathology and Gynecopathology, Erasme University Hospital, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium E‐mail: jenoel@ulb.ac.be Search for other works by this author on: Oxford Academic Google Scholar G. Debusschere, G. Debusschere Departments of Dermatopathology and Gynecopathology, Erasme University Hospital, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium E‐mail: jenoel@ulb.ac.be Search for other works by this author on: Oxford Academic Google Scholar D. Parent D. Parent Departments of Dermatopathology and Gynecopathology, Erasme University Hospital, Free University of Brussels, 808 route de Lennik, 1070 Brussels, Belgium E‐mail: jenoel@ulb.ac.be Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 2, 1 August 2005, Pages 457–458, https://doi.org/10.1111/j.1365-2133.2005.06751.x Published: 01 August 2005
IMPROVED SPACE-TIME QUANTITATION OF SEGMENTAL THALLIUM-201 MYOCARDIAL SCINTIGRAMS
Authors: K. Van Train, E. Garcia, J. Maddahl, D. Brown, S. Hulse, A. Waxman, O. Berman
Journal: Clinical Nuclear Medicine (1981)

Train, K. Van; Garcia, E.; Maddahl, J.; Brown, D.; Hulse, S.; Waxman, A.; Berman, O. Author Information
Treatment of Parvovirus B19–Associated Polyarteritis Nodosa with Intravenous Immune Globulin
Authors: Manuelle Viguier, Loic Guillevin, Liliane Laroche
Journal: New England Journal of Medicine (2001)

The article by Mechanic et al. (Jan.18 issue) 1 challenges the prevailing wisdom that the increased penetration of managed care is associated with a decrease in the length of patients' office visits with physicians.The data to support their conclusions were derived from the National Ambulatory Medical Care Survey (NAMCS) and the monitoring system of the American Medical Association (AMA).Although the numbers superficially suggest that more time is being spent with patients, no measure of the time physicians actually spent talking with and examining patients could be obtained from these studies.Although there may have been an "upward trend in the length of visits for both primary and specialty care," I would suggest that the apparent increase in duration may be accounted for by the time spent in the completion of paperwork.If such a study were performed in academic medical centers, such as the one in which I practice, it would find a dramatic increase in the time physicians spend documenting, and frequently duplicating, the work and findings of trainees.As pediatricians, we espouse emphasizing the quality, not the quantity, of parents' time with children.We should do the same for physicians' time with patients.