tbuckley/cabot-search huggingface dataset:
Abstract 3318: Molecular targeting of brain tumor stem cells
Authors: Christine E. Eyler, Michael T. Forrester, Jennifer M. MacSwords, Qiulian Wu, Katherine M. LaFiura, Justin D. Lathia, Andrew E. Sloan, Jeongwu Lee, Roger E. McLendon, Anita B. Hjelmeland, Jeremy N. Rich
Journal: Cancer Research (2010)

Abstract Although current therapeutic strategies for malignant gliomas are non-specifically directed against the tumor bulk, increasing evidence suggests that a single glioma contains a range of phenotypically disparate cell populations with differential capacity for tumor maintenance and initiation. Recent work in brain tumors suggests the existence of cellular sub-populations (known as cancer stem cells, or CSCs) that possess stem cell-like behaviors and a potent capacity for tumor initiation in transplantation assays relative to non-CSCs. Specifically targeting the highly tumorigenic CSCs has the potential to improve the prognosis of malignant glioma patients, but many molecularly-directed anti-CSC agents may also compromise the survival of normal neural stem cells due to molecular similarities between CSCs and normal stem cells. Here we demonstrate that malignant glioma CSCs express high levels of a particular protein relative to non-CSCs. Glioma CSC growth and tumorigenic capacity were abrogated by multiple strategies interfering with the expression and activity of this protein, including RNA interference, pharmacological inhibition, and heterologous expression of a prokaryotic enzyme that specifically consumes the enzymatic product of this critical protein. Importantly, tumor growth was inhibited by systemic treatment of xenograft-bearing mice with a well-studied small molecule inhibitor of this protein that has already demonstrated low toxicity in clinical trials for other diseases. Though the activity of this protein appears critical for the maintenance of highly tumorigenic glioma CSCs, our examination of both normal human neural progenitor cells and neural stem cells derived from genetically disrupted mice indicate no substantial role for this protein in normal neural stem cells. Our findings identify a novel glioma therapeutic target with a negligible role in normal neural stem cells, suggesting clinical utility for selective inhibitors of this CSC-specific molecular target. 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 3318.
Adjuvant Chemotherapy for Breast Cancer
Authors: Harvey N. Himel
Journal: JAMA (1986)

The use of adjuvant chemotherapy for treating patients with operable breast cancer remains a worldwide controversy. Using the data from published randomized control trials with a minimum two-year follow-up, pooled estimates of relapse-free survival rates and overall survival rates were calculated. Relapse-free survival rates were improved by 12.5% (95% confidence interval [CI] ±4.5%) at three years and by 8% (CI ±6%) at five years, with studies using multiple agents showing a greater effect. A significant advantage was also present in overall survival rates at three years, but only for studies involving multiple agents (4% ±3.5%). Results from combining data for other types of trials were inconclusive. The use of this method is presented to illustrate its value as an explicit and systematic one for combining data from several randomized control trials in assessing a therapeutic controversy. (<i>JAMA</i>1986;256:1148-1159)
Prospective study of factors predicting outcome of transdermal nicotine treatment in smoking cessation
Authors: S G Gourlay, A Forbes, T Marriner, D Pethica, J J McNeil
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective:</b> To assess the factors associated with cessation of smoking with transdermal nicotine and brief behavioural counselling. <b>Design:</b> Interviews, treatment, and follow up for 26 weeks. <b>Subjects:</b> 1481 subjects recruited by mass media publicity who smoked &gt;=15 cigarettes a day and were motivated to stop smoking. Interventions - Twelve weeks9 treatment with transdermal nicotine and brief behavioural counselling at monthly visits. <b>Main outcome measure:</b> Sustained smoking cessation for the 28 days before the visit at week 26 verified by expired carbon monoxide concentrations. The logistic regression analysis included all subjects. <b>Results:</b> Most subjects were dependent on nicotine, and the mean (SD) number of cigarettes smoked a day was 32 (12). Overall, 316/1481 subjects (21.3%) stopped smoking. Factors associated with stopping were being male (adjusted odds ratio 2.0; 95% confidence interval 1.5 to 2.7), age &gt;=40 years (1.5; 1.1 to 2.0), living with a spouse or partner (1.5; 1.1 to 2.1), motivation ("want to quit" 1.7; 1.2 to 2.3), and concern about weight gain (1.7; 1.3 to 2.2). Negative associations were smoking marijuana (0.4; 0.2 to 0.8) and the presence of other smokers in the household (0.8; 0.6 to 0.9). Almost all subjects who smoked three or more cigarettes in the first four weeks of treatment resumed smoking in the long term (525/547, 96%). <b>Conclusions:</b> Age, sex, marital status (living with a spouse or partner), motivation, concern about weight gain, recent marijuana smoking, and other smokers in the household were baseline factors associated with differences in outcome of smoking cessation attempts. Smoking three or more cigarettes in the first few weeks after stopping strongly predicted long term relapse.
Natural-orifice transluminal endoscopic surgery: from the laboratory to routine implementation – an editor’s point of view
Authors: T. Ponchon
Journal: Endoscopy (2010)

Papers in the June 2010 and the present issues of Endoscopy illustrate the problems that are posed by the development of natural-orifice transluminal endoscopic surgery (NOTES), and by the publication of the results of this technique. The first of these papers, by Fritscher-Ravens et al. [1], published in the June issue, focuses on the development of NOTES thoracoscopy in animals by crossing the esophageal wall, which has always been regarded as inviolable because of the risks of infection. The second paper, by Linke et al. [2], in this month’s issue, is already on routine application of hybrid NOTES surgery. Furthermore, also in this issue, A. Fritscher-Ravens [3] reports an application of technology derived from NOTES for the treatment of an esophageal leak, an occurrence which is frequently very challenging.
The Emergence in Taiwan of Fluoroquinolone Resistance in<i>Salmonella enterica</i>Serotype Choleraesuis
Authors: Cheng-Hsun Chiu, Tsu-Lan Wu, Lin-Hui Su, Chishih Chu, Ju-Hsin Chia, An-Jing Kuo, Maw-Sheng Chien, Tzou-Yien Lin
Journal: New England Journal of Medicine (2002)

serotype choleraesuis is a cause of serious systemic infections. Because fluoroquinolones are the drug of choice for the treatment of severe salmonella infections, the emergence and dissemination of fluoroquinolone-resistant S. enterica serotype choleraesuis have clinical consequences.
Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity
Authors: Dallas B. Flies, Xue Han, Tomoe Higuchi, Linghua Zheng, Jingwei Sun, Jessica Jane Ye, Lieping Chen
Journal: Journal of Clinical Investigation (2014)

T cell activation is regulated by the interactions of surface receptors with stimulatory and inhibitory ligands. Programmed death-1 homolog (PD-1H, also called VISTA) is a member of the CD28 family of proteins and has been shown to act as a coinhibitory ligand on APCs that suppress T cell responses. Here, we determined that PD-1H functions as a coinhibitory receptor for CD4⁺ T cells. CD4⁺ T cells in mice lacking PD-1H exhibited a dramatically increased response to antigen stimulation. Furthermore, delivery of a PD-1H-specific agonist mAb directly inhibited CD4⁺ T cell activation both in vitro and in vivo, validating a coinhibitory function of PD-1H. In a murine model of acute hepatitis, administration of a PD-1H agonist mAb suppressed CD4⁺ T cell-mediated acute inflammation. PD-1H-deficient animals were highly resistant to tumor induction in a murine brain glioma model, and depletion of CD4⁺ T cells, but not CD8⁺ T cells, promoted tumor formation. Together, our findings suggest that PD-1H has potential as a target of immune modulation in the treatment of human inflammation and malignancies.
925 COMPARISON OF THE USEFULNESS OF THREE NOVEL OUTCOME PREDICTING MODELS BASED ON DATA MINING METHODS FOR PATIENTS WITH ACUTE LIVER FAILURE
Authors: N. Nakayama, M. Oketani, Y. Kawamura, M. Inao, S. Nagoshi, K. Fujiwara, H. Tsubouchi, S. Mochida
Journal: Journal of Hepatology (2011)
Reproducibility of the skin prick test
Authors: I. VOHLONEN, E. O. TERHO, A. KOIVIKKO, T. VANTO, A. HOLMÉN, O. P. HEINONEN
Journal: Allergy (1989)

Reproducibility of the skin prick method of testing for allergy was studied in 20 subjects examined by four nurses. Hypodermic needles were used for pricking and the test panel included a histamine control, a diluent control, and nine allergens. The reproducibility of the method was best when the size of the weal reaction caused by an allergen was expressed as the geometric area of the weal. When the weal reaction was expressed as the ratio of the weal reaction caused by an allergen to that caused by histamine, the reproducibility of the method was decreased considerably. When the ratios were further classified into three class ratings, reproducibility was very low. The reduction in reproducibility was due to the low reproducibility of histamine reactions. According to these results, at least in epidemiological studies the weal reactions should be expressed as geometric areas. In clinical practice it might also be preferable to express prick test results as the diameters of the weals without adjusting them by histamine reactions.
THE STUDENTS' UNIT MEDICAL LABORATORY
Authors: CHAUNCEY D. LEAKE
Journal: JAMA (1924)

Within recent years, considerable interest has arisen regarding the correlation of the physical aspects of the medical school building with the problems of teaching medicine. Various attempts to solve these problems have been suggested by Dean Meader,<sup>1</sup>of the University of Colorado School of Medicine, and Dean Robinson,<sup>2</sup>of the Vanderbilt University Medical Department. The essential point of both these plans has been the attempt to bring about a closer relation between the laboratory work and the clinical work. The problems of medical education have been discussed in a series of three papers<sup>3</sup>in a recent issue ofThe Journal. It is the general consensus of the authors of these papers that this correlation between the laboratory work of the first two years and the clinical work of the last two years is an absolute necessity. The architectural attempts that have been made to bring about a
Antibody Fusion Proteins: Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox
Authors: Robert J. Kreitman, Ira Pastan
Journal: Clinical Cancer Research (2011)

Recombinant immunotoxins are fusion proteins that contain the cytotoxic portion of a protein toxin fused to the Fv portion of an antibody. The Fv binds to an antigen on a target cell and brings the toxin into the cell interior, where it arrests protein synthesis and initiates the apoptotic cascade. Moxetumomab pasudotox, previously called HA22 or CAT-8015, is a recombinant immunotoxin composed of the Fv fragment of an anti-CD22 monoclonal antibody fused to a 38-kDa fragment of Pseudomonas exotoxin A, called PE38. Moxetumomab pasudotox is an improved, more active form of a predecessor recombinant immunotoxin, BL22 (also called CAT-3888), which produced complete remission in relapsed/refractory hairy cell leukemia (HCL), but it had a <20% response rate in chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL), diseases in which the leukemic cells contain much lower numbers of CD22 target sites. Compared with BL22, moxetumomab pasudotox is up to 50-fold more active on lymphoma cell lines and leukemic cells from patients with CLL and HCL. A phase I trial was recently completed in HCL patients, who achieved response rates similar to those obtained with BL22 but without dose-limiting toxicity. In addition to further testing in HCL, moxetumomab pasudotox is being evaluated in phase I trials in patients with CLL, B-cell lymphomas, and childhood ALL. Moreover, protein engineering is being used to increase its activity, decrease nonspecific side effects, and remove B-cell epitopes.
Abstract 893: Contrast Medium-Induced Renal Damage is Tightly Associated with Endothelial Injury in Patients
Authors: Kazuko Tajiri, Hidekazu Maruyama, Satoshi Sakai, Noritake Shimojo, Hideaki Aihara, Masae Endo, Takumi Saito, Satoru Kawano, Shigeyuki Watanabe, Kazutaka Aonuma
Journal: Circulation (2008)

Background: Contrast-induced nephropathy (CIN) remains a common complication of radiographic procedures. We hypothesized that endothelial dysfunction is the main cause of CIN. To clarify whether contrast medium-induced renal damage is associated with endothelial injury, we measured microparticles derived from endothelial cells as markers of endothelial injury. Circulating microparticles are shed from cell surface respond to cell activation and apoptotic stimuli, reflecting the condition of damaged cells. Methods: Renal function of 35 adult patients was analyzed before and after the use of contrast medium for coronary angiography. Parameters for renal function and urinary 15-isoprostane F2t, a specific marker of oxidative stress were measured before and after radiocontrast administration. Flow cytometry was used to count circulating CD34 + microparticles, which is regarded as one of markers for endothelial damage. Results: The decrease of estimated glomerular filtration rate positively correlated with the amount of contrast medium (r=0.427; P=0.013). Urinary N-acetyl-beta-D-glucosaminidase, a marker of renal tubular injury, was increased after angiography (from 7.6+/− 6.8 to 9.1 +/− 6.0 U/g-CRE, P=0.011). Furthermore, urinary 15-isoprostane F2t positively correlated with the volume of contrast medium (r=0.421; P=0.012). CD34+ microparticle was significantly increased after angiography (1.3-fold increased from basal level, P=0.0017). The increase of CD34+ microparticle was associated with the insult of contrast medium, but not of the amount. Conclusion: Radiocontrast impaired renal function in accordant with the increase of oxidative stress. The release of CD34+ microparticle was also increased by use of radiocontrast. These data suggest that CIN is tightly associated with endothelial injury mediated by radiocontrast-induced oxidative stress.
Frederic Basil Stileman Barkworth Paul Brian Counsell Samuel Wolfe Hirschmann Mohammed Shahbaaz Khan Robert Kenneth McAll Leslie Alexander McDowell George Hay Marshall Walter John Murfin Bruce Drummond Taylor Scott Nigel John Wilson
Authors: I. Brown, J. Surtees, G. Black, P N Hirschmann, J. Haer, M. Crowley, G E O. Williams, J. Black, D. Murfin, M. Walker-Kinnear, M Hull, R Delaney, G Pritchard
Journal: BMJ (2001)

He was resident medical officer at the Mildmay Mission Hospital in east London.He served in the Royal Army Medical Corps as graded radiologist, mainly in Palestine and North Africa, and began in general practice just before the start of the NHS.He was sustained by a deep seated Christian faith, and played a
Physiological aspects of menopausal hot flush.
Authors: D W Sturdee, K A Wilson, E Pipili, A D Crocker
Journal: BMJ (1978)

Eighteen hot flushes experimenced by eight menopausal women were studied and compared with the effects of warming in six premenopausal women. The hot flushes were associated with an acute rise in skin temperature, peripheral vasodilatation, a transient increase in heart rate, fluctuations in the electrocardiographic (ECG) baseline, and a pronounced decrease in skin resistence. Although premenopausal women had greater maximum increases in skin temperature and peripheral vasodilatation, they showed a much smaller decrease in skin resistance and no changes in heart rate or ECG baseline. These findings suggest that the onset of the hot flush is associated with a sudden and transient increase in sympathetic drive. Further investigations may lead to the development of a more specific alternative to oestrogen for relieving menopausal hot flushes.
Echo-phonocardiographic and contrast studies in conditions associated with systemic arterial trunk overriding the ventricular septum: truncus arteriosus, tetralogy of Fallot, and pulmonary atresia with ventricular septal defect.
Authors: J L Assad-Morell, J B Seward, A J Tajik, D J Hagler, E R Giuliani, D G Ritter
Journal: Circulation (1976)

Echocardiography was performed in 62 patients--20 with truncus arteriosus, 14 with tetralogy of Fallot, and 28 with pulmonary atresia with ventricular septal defect. Features common in all three groups were: large single systemic arterial trunk overriding the ventricular septum, mitral-semilunar continuity, large right ventricular dimension, and normal septal motion. Indocyanine green contrast flow patterns were similar and were most helpful in detecting an associated atrial septal defect and in studying the timing and pattern of right-to-left shunting. Echo-phonocardiographic studies revealed that the ejection click coincided with the point of maximal opening of aortic or truncal valve. Left atrial dimension was measured in 55 patients and was normal or small in 41 patients and large in 14 patients. Our observations indicate that left atrial dimension provides a good index of pulmonary flow and can help differentiate those patients with increased pulmonary flow and can help differentiate those patients with increased pulmonary flow (truncus arteriosus) from those patients with reduced pulmonary flow (tetralogy of Fallot and pulmonary atresia with associated ventricular septal defect).
Lack of support for a genetic association of the XBP1 promoter polymorphism with bipolar disorder in probands of European origin
Authors: Sven Cichon, Silvia Buervenich, George Kirov, Nirmala Akula, Albena Dimitrova, Elaine Green, Johannes Schumacher, Norman Klopp, Tim Becker, Stephanie Ohlraun, Thomas G Schulze, Monja Tullius, Magdalena M Gross, Lisa Jones, Stefan Krastev, Ivan Nikolov, Marian Lindsay Hamshere, Ian Richard Jones, Piotr M. Czerski, Anna Leszczynska-Rodziewicz, Pawel Kapelski, Ann Van Den Bogaert, Thomas Illig, Joanna Hauser, Wolfgang Maier, Wade Berrettini, William Byerley, William Coryell, Elliot S. Gershon, John R. Kelsoe, Melvin G. McInnis, Dennis L. Murphy, John I. Nurnberger, Theodore Reich, William Scheftner, Michael Conlon O'Donovan, Peter Propping, Michael John Owen, Marcella Rietschel, Markus M. Nöthen, Francis J. McMahon, Nicholas John Craddock
Journal: Nature Genetics (2004)
Abstract 1795: The Combination of Paclitaxel and Gefitinib Inhibits Endometrial Cancer Cells by Inducing Mitotic Catastrophe: Proof of Principle for Dual Therapy in Endometrial Cancer
Authors: Xiangbing Meng, Laura L. Laidler, Lina Albitar, Anna M. Holmes, Donghai Dai, Thomas E. Buekers, David P. Bender, Kimberly K. Leslie
Journal: Cancer Research (2010)

Abstract Serous uterine endometrial cancer is a lethal disease for which new therapeutic regimens are urgently needed. Combinations of chemotherapeutic agents and small molecule growth factor inhibitors have demonstrated activity in cancers from other sites. Our objective was to determine whether such a combination could be active in serous endometrial cancer cells. The effects of the EGFR inhibitor gefitinib (ZD1839, Iressa) alone, paclitaxel alone, and the combination of both agents on the cell cycle and on cell proliferation were studied using Hec50co cells, a validated model for type II serous endometrial cancer with absent p53. First, we established the IC50 for paclitaxel alone (14 nM) compared to that of paclitaxel and gefitinib in combination (1.3 nM). This 10-fold reduction in the IC50 with dual therapy yielded a combination index of 0.25, strongly suggesting that the paclitaxel and gefitinib combination resulted in synergistic growth inhibition. Sixty-seven percent of the cells treated with paclitaxel and gefitinib arrested in the G2/M phase. This arrest of the cell cycle at G2/M with combination therapy was significantly greater than with single agent treatment alone (p &amp;lt; 0.001) and was associated with inhibition of p38 phosphorylation and the induction of CDC25C phosphatase and Cyclin B1. When induced, these factors abrogate the G2/M checkpoint and result in rapid, premature progression to M phase; this mechanism is particularly active in the setting of absent p53. With rapid progression into M, the cells were highly sensitive to paclitaxel and were killed by the mechanism of mitotic catastrophe. Similar findings were observed in the same cells treated with the combination of paclitaxel and a specific inhibitor of p38, SB203580. Our study suggests that inhibition of EGFR or downstream p38 pathway can abrogate the mitotic stress checkpoint induced by cytotoxic agents targeting microtubules such as paclitaxel. These findings suggest a new therapeutic strategy for the treatment of serous endometrial carcinoma worthy of clinical confirmation. 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 1795.
Metabolic Syndrome as a Predictor of All-Cause and Cardiovascular Mortality in Type 2 Diabetes
Authors: Graziella Bruno, Franco Merletti, Annibale Biggeri, Giuseppe Bargero, Stefania Ferrero, Cristina Runzo, Stefano Prina Cerai, Gianfranco Pagano, Paolo Cavallo-Perin
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization–defined metabolic syndrome, independent of conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS—During the follow-up (1991–2001), 1,565 patients were regularly examined with centralized measurements of HbA1c. The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESULTS—At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6–77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16–7.33), independent of other risk factors. CONCLUSIONS—We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.
Zomepirac-Induced Serum Sickness
Authors: Reza Kiani
Journal: JAMA (1983)

Two patients, after several weeks of zomepirac sodium use, experienced acute toxic eruption, fever, lymphadenopathy, arthralgias, angioedema of the hands, and eosinophilia. We believe that these cases represent type 3 allergic reactions to zomepirac.