tbuckley/cabot-search huggingface dataset:
Abstract 24: Labeling of oxidizable proteins with a photoactivatable analog of the antitumor agent DMXAA and evidence for redox signaling in its mode of action
Authors: Lai-Ming Ching, Liang-Chuan S. Wang, Romy Brauer, David J.A Bridewell, Kimiora Henare, Brian D. Palmer
Journal: Cancer Research (2010)

Abstract DMXAA (5,6-dimethylxanthenone-4-acetic acid) is in late stages of clinical development as a tumor vascular disrupting agent. The signalling pathway(s) and molecular target(s) for this drug are still undefined. As an approach towards identifying potential targets for DMXAA, a tritiated azido-analog of DMXAA is used in the studies here to probe for cellular binding proteins. Unexpectedly, over 20 proteins were photo-affinity labelled from the cytosolic protein extracts from murine spleen cells and the RAW 264.7 murine macrophage-like cell line. While no protein domain, fold or binding site for a specific ligand was found to be shared by all the candidate proteins, almost all were noted to be oxidisable proteins, implicating a role for redox cycling in the action of DMXAA. Consistent with this hypothesis, we showed that DMXAA caused an accumulative increase in concentrations of reactive oxygen species (ROS) in RAW 264.7 cells over the first two hours. This increase in ROS was suppressed in the presence of the anti-oxidant, N-acetyl-L-cysteine, which also suppressed DMXAA-induced cytokine production in the RAW 264.7 cells with no effects on cell viability. SiRNA knock-down in RAW 264.7 cells of one of the photolabelled proteins, superoxide dismutase 1, an ROS scavenger resulted in an increase in tumour necrosis factor-alpha production in response to DMXAA compared with controls treated with transfection reagent alone, or with unrelated siRNA molecules. Knock-down of two other photoaffinity labelled proteins which do not have direct ROS scavenging properties, thioredoxin and protein disulfide isomerase 6, had no significant effect on tumour necrosis factor-alpha production. The results from these three lines of study have led us to speculate on a role of modulation of redox signalling in cytokine induction by DMXAA. 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 24.
Quinidine-Induced Hypoprothrombinemic Hemorrhage in Patients on Chronic Warfarin Therapy
Authors: JAN KOCH-WESER
Journal: Annals of Internal Medicine (1968)

In three patients whose prothrombin-complex activity was being chronically maintained in the therapeutic range by warfarin sodium, the institution of quinidine therapy was followed within 6 to 10 days by excessive hypoprothrombinemia and hemorrhages. No other causes for the sudden drop in prothrombin level could be found. In two patients the one-stage prothrombin time remained slightly prolonged when warfarin was stopped and quinidine continued. When the third patient discontinued quinidine, the original dose of warfarin was again required to lower the prothrombin content into the therapeutic range. Both quinidine and quinine can depress the prothrombin-complex activity of normal individuals. They act synergistically with warfarin and other oral anticoagulants to depress vitamin K-sensitive hepatic clotting factor synthesis. Their use in patients on anticoagulant therapy can precipitate serious hypoprothrombinemic hemorrhages. When quinidine therapy is started in such patients, their prothrombin time must be closely followed, and a reduction in anticoagulant requirements should be anticipated.
A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer
Authors: Pierre Farmer, Hervé Bonnefoi, Pascale Anderle, David Cameron, Pratyakasha Wirapati, Véronique Becette, Sylvie André, Martine Piccart, Mario Campone, Etienne Brain, Gaëtan MacGrogan, Thierry Petit, Jacek Jassem, Frédéric Bibeau, Emmanuel Blot, Jan Bogaerts, Michel Aguet, Jonas Bergh, Richard Iggo, Mauro Delorenzi
Journal: Nature Medicine (2009)
Update: novel influenza A (H1N1) virus infection - Mexico, March-May 2009.
Authors: J. A. Cordova, M. Hernandez, H. Lopez-Gatell, I. Bojorquez, E. Palacios, G. Rodriguez, B. de la Rosa, R. Ocampo, C. Alpuche, R. Flores, J. E. Hernandez, J. Tustin, K. Watkins, T. L. Stuart, T. Kuschak, U. Ströher, G. Soule, B. Balcewich, E. Azziz-Baumgartner, K. Lafond, J. Mott, F. Mahoney, T. Uyeki, M. McCarron, A. Mounts, M. A. Widdowson
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure
Authors: C. Beauloye, L. Bertrand, S. Horman, L. Hue
Journal: Cardiovascular Research (2011)

Heart failure is a progressive muscular disorder leading to a deterioration of the heart characterized by a contractile dysfunction and a chronic energy deficit. As a consequence, the failing heart is unable to meet the normal metabolic and energy needs of the body. The transition between compensated left ventricular hypertrophy and the de-compensated heart is multifactorial, although metabolic disturbances are considered to play a significant role. In this respect, the AMP-activated protein kinase (AMPK) could be a potential target in heart failure development. AMPK senses the energy state of the cell and orchestrates a global metabolic response to energy deprivation. We briefly review here the current knowledge about the chronic energy deficit of the failing heart, as well as the role of AMPK in energy homeostasis and in the control of non-metabolic targets in relation to cardiac hypertrophy and heart failure. The relative importance of energetic and non-metabolic effects in the potential cardioprotective action of AMPK is discussed.
The Water Factor
Authors: Henry A. Schroeder
Journal: New England Journal of Medicine (1969)

In the early spring of 1957 Kobayashi showed me some data linking a quality of river water in Japanese prefectures with death rates from cerebral hemorrhage, the first cause of death in Japan. There appeared to be a direct relation between deaths from this cause and the sulfate-bicarbonate ratio of water by prefecture.1 This ratio is an index of acidity. All Japanese river water is soft — less than 42 ppm hardness.2 Examination of these data showed the relation to be statistically valid; death rates from heart disease were low in Japan and bore no correlation with any quality of . . .
TIPS and Variceal Bleeding
Authors: Andres T. Blei
Journal: Annals of Internal Medicine (1992)

Letters1 August 1992TIPS and Variceal BleedingAndres T. Blei, MDAndres T. Blei, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-3-266_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:I read with interest the article by Ring and colleagues (1) on the potential benefits of transjugular intrahepatic portosystemic shunts (TIPS) for control of variceal bleeding in patients with poor liver function and uncontrollable hemorrhage or for those awaiting liver transplantation. The study, however, lacks precision in that the article does not mention how portal pressure was measured. Values are presented in centimetres of water; how was the pressure device calibrated? Were permanent records made of the pressure tracings? How can values of hepatic vein pressure not have been included when the pressure gradient across the liver...References1. RingLakeRobertsGordonLaBergeRead EJJLJA. Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation. Ann Intern Med. 1992; 116:304-9. LinkGoogle Scholar2. MyersTaylor JW. An estimation of portal venous pressure by occlusive catheterization of a hepatic venule. J Clin Invest. 1951;30: 662-70. Google Scholar3. SarfehRypinsMason IEG. A systematic appraisal of portacaval H-graft diameters: clinical and hemodynamic perspectives. Ann Surg. 1986;204:356-63. CrossrefMedlineGoogle Scholar4. CoySrivastavaGottsteinButterworthBlei DAJRA. Post-operative course after portacaval anastomosis in rats is determined by the portacaval pressure gradient. Am J Physiol. 1991;261:G1072-8. MedlineGoogle Scholar5. Garcia-TsaoGroszmannFisherConnAtterburyGlickman GRRHCM. Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology. 1985;5:419-24. CrossrefMedlineGoogle Scholar1. RingLakeRobertsGordonLaBergeRead EJJRJA. Using transjugular intrahepatic portosystemic shunts to control variceal bleeding before liver transplantation. Ann Intern Med. 1992; 116:304-9. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Andres T. Blei, MDAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPercutaneous transhepatic obliteration-related procedures for isolated gastric varices: experience of three casesPercutaneous transhepatic obliteration and percutaneous transhepatic sclerotherapy for intractable hepatic encephalopathy and gastric varices improves the hepatic function reserveTransjugular intrahepatic portosystemic shunts: Impact on liver transplantation 1 August 1992Volume 117, Issue 3Page: 266-266KeywordsHemorrhageLiverLiver transplantationVeins ePublished: 1 December 2008 Issue Published: 1 August 1992 PDF downloadLoading ...
Prenatal Diagnosis of Cystinosis
Authors: Jerry A. Schneider, Francoise M. Verroust, Wolfgang A. Kroll, A. Julian Garvin, Edgar O. Horger, Vernon G. Wong, Gerald S. Spear, Cecil Jacobson, Ocean L. Pellett, Frederikus L. A. Becker
Journal: New England Journal of Medicine (1974)

We diagnosed cystinosis in an 18-week-old fetus on the basis of an increased content of nonprotein cystine in cultured amniotic-fluid cells. These cells did not contain cystine crystals, and the cystine concentration of cell-free amniotic fluid was normal. Thus, in utero diagnosis can only be made by measurement of the nonprotein cystine content of cultured amniotic-fluid cells. The pregnancy was terminated by hysterotomy. No cystine crystals were observed in any organ. The only tissue that was abnormal by phase or light microscopy was the retinal-pigment epithelium, in which vacuolization was observed. The diagnosis was confirmed because the nonprotein cystine content of the liver, placenta, kidney, thymus and spleen was 50 to 100 times greater than in control fetuses. Cell cultures were established from nine fetal organs, and all contained increased amounts of nonprotein cystine. (N Engl J Med 290:878–882, 1974)
Involvement of endothelin in the regulation of human vascular tonus. Potent vasoconstrictor effect and existence in endothelial cells.
Authors: T Miyauchi, Y Tomobe, R Shiba, T Ishikawa, M Yanagisawa, S Kimura, Y Sugishita, I Ito, K Goto, T Masaki
Journal: Circulation (1990)

Endothelin, a recently discovered endothelium-derived peptide, has been reported to produce potent vasoconstriction in various vessels of experimental animals. To study the involvement of endothelin in the regulation of vascular tonus in humans, isolated human mesenteric arteries were investigated by both pharmacological and immunohistochemical methods. The vasoconstrictor action of endothelin-1 was examined on ring segments of human mesenteric arteries. Endothelin-1 induced a slowly developing and sustained contraction, with an EC50 value (half-maximal effective concentration) of 2.9 x 10(-9) M, two orders of magnitude smaller than that of norepinephrine (EC50 of 3.9 x 10(-7) M), indicating that the vasoconstrictor action of endothelin-1 is about 100 times more potent than that of norepinephrine. The contractile effect of endothelin-1 was affected neither by adrenergic, cholinergic, histaminergic, nor serotonergic antagonists, nor by inhibitors of arachidonic acid metabolism. The vasoconstrictor response to endothelin-1 was effectively antagonized by nicardipine, a dihydropyridine Ca2+ channel blocker. Endothelin-1 profoundly augmented contractile response to Ca2+ in partially depolarized tissues. Immunohistochemical studies revealed for the first time that endothelin-like immunoreactivity was localized in endothelial cells of human mesenteric artery. The results of the present study indicate that endothelin-1 is one of the most potent vasoconstrictors in the human mesenteric artery and that it induces vasoconstriction via an ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels. Since endothelin-1 can be located in human endothelial cells, it may play an important physiological or pathophysiological role.
Assessing the Risks of Genotoxicity in the Therapeutic Development of Induced Pluripotent Stem Cells
Authors: So Gun Hong, Cynthia E Dunbar, Thomas Winkler
Journal: Molecular Therapy (2012)

Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced. Induced pluripotent stem cells (iPSCs) have great potential for regenerative medicine as well as for basic and translational research. However, following the initial excitement over the enormous prospects of this technology, several reports uncovered serious concerns regarding its safety for clinical applications and reproducibility for laboratory applications such as disease modeling or drug screening. In particular, the genomic integrity of iPSCs is the focus of extensive research. Epigenetic remodeling, aberrant expression of reprogramming factors, clonal selection, and prolonged in vitro culture are potential pathways for acquiring genomic alterations. In this review, we will critically discuss current reprogramming technologies particularly in the context of genotoxicity, and the consequences of these alternations for the potential applications of reprogrammed cells. In addition, current strategies of genetic modification of iPSCs, as well as applicable suicide strategies to control the risk of iPSC-based therapies will be introduced.
Ca <sup>2+</sup> -Induced Current Oscillations in Rabbit Ventricular Myocytes
Authors: Michael A. Laflamme, Peter L. Becker
Journal: Circulation Research (1996)

Abstract Transient currents are activated by spontaneous Ca 2+ oscillations in rabbit ventricular myocytes. We investigated the ionic basis for these transient currents under conditions in which K + currents would be expected to be blocked. Holding cells under voltage clamp at positive potentials leads to a rise in intracellular Ca 2+ via reversal of the Na + -Ca 2+ exchanger and subsequently to the initiation of spontaneous Ca 2+ transients, presumably from a Ca 2+ -overloaded sarcoplasmic reticulum. The current transients associated with these Ca 2+ transients reversed at about +10 to +15 mV under conditions of approximately symmetrical Cl − . In the absence of Cl − , this current was inward at all potentials examined over the range from −88 to +72 mV, consistent with a Na + -Ca 2+ exchanger current. In the absence of Na + , the repetitive spontaneous Ca 2+ transients could be initiated by a brief train of depolarizations to activate the inward Ca 2+ current. Under such conditions, the current was found to reverse at −3 mV when the equilibrium potential of Cl − (E Cl ) was −2 mV, and the reversal potential shifted to −32 mV when internal Cl − was lowered, to make E Cl −33 mV. Thus, in the absence of Na + , it appears that the current is exclusively a Ca 2+ -activated Cl − current. There is no evidence to indicate the presence of a Ca 2+ -activated cationic conductance. Further, our results demonstrate that the Ca 2+ -activated Cl − conductance can carry inward current at potentials more negative to E Cl in rabbit ventricular myocytes and is therefore likely to contribute to the arrhythmogenic delayed afterdepolarizations that occur in Ca 2+ -overloaded cells.
Age discrimination must stop, says royal college
Authors: A Tonks
Journal: BMJ (1994)

Old people in Britain are poorly served by a health service riddled with age discrimination, patchy services, and poor relationships among hospital specialists charged with their care, says a new report. It describes how some hospitals systematically discriminate against elderly people by allocating them to wards on the basis of age rather than illness or other needs. Other elderly people, claims the report, are denied lifesaving treatment because some coronary care units and intensive care units refuse to admit patients over a certain age - usually 75.

The report, compiled by the Royal College of Physicians, warns that separating services for elderly people …
Surgical Management of Oncogeriatric Patients
Authors: Riccardo A. Audisio, Andrew P. Zbar, Michael T. Jaklitsch
Journal: Journal of Clinical Oncology (2007)

Major changes are taking place at a great pace in modern medicine, and surgical oncologists are at the forefront when new skills are to be tested and implemented. Perhaps the most significant change we are facing relates to the aging of our population, with most solid tumors presenting at age 70 years (+/- 5 years). The demographics and epidemiological details are covered in the appropriate sections of this special issue, but it is important to realize how such a shift influences our day-to-day practice. These principally are occurring in improved anesthetic care, minimally invasive surgery, nonoperative therapies, risk assessment, and quality-of-life estimates.
The Pediatric Nurse-Practitioner Program
Authors: Harold W. Keairnes
Journal: JAMA (1968)

<h3>To the Editor:—</h3> The pediatric nurse-practitioner, as described by Silver et al (<b>204</b>:298, 1968) continues the trend to use more and more nursing and paramedical personnel to carry out tasks that were formerly done by the physician. The article simultaneously continues the trend which says that "if it is new it must be good." This philosophy must be challenged by the burgeoning techniques of health services research. The philosophy that adding more and more personnel, or increasing the number of dollars expended, or doing more of anything will result in higher quality and more efficient medical care must be subject to critical evaluation. In the program described, there is no evidence to prove that the quality of care is better, the cost of care is less, (3) physicians' efficiency is increased, that patients are healthier, or that parents are happier. Innovations in the delivery of health services should now
Diabetes and Associated Risk Factors Among Native Americans
Authors: Ben Muneta, Jeff Newman, Scott Wetterall, John Stevenson
Journal: Diabetes Care (1993)

OBJECTIVES To estimate the prevalence of diabetes and related risk factors among Native Americans. RESEARCH DESIGN AND METHODS We used 1988–1989 data from the Behavioral Risk Factor Surveillance System to calculate the overall, age-adjusted prevalence of diabetes, obesity, sedentary life-style, hypertension, and smoking among Native Americans. The SESUDAAN software package was used to derive confidence intervals. RESULTS The prevalence of diabetes was 11.6% among the 768 Native American Behavioral Risk Factor Surveillance System respondents (95% confidence interval 7.8–15.4) and 4.7% among the 121,986 white respondents (95% confidence interval 4.6–4.8). The age-adju ted prevalence of diabetes was 2.5 times higher among Native Americans than among whites. The prevalence of obesity was higher among Native Americans (34.4; 95% confidence interval 31.7–37.1) than among whites (23.9%; confidence interval 23.7–24.1). The prevalences of sedentary lifestyle (58%), hypertension (16%), and smoking (28%) were similar among both populations. CONCLUSIONS The Behavioral Risk Factor Surveillance System may prove as a useful tool for surveying Native Americans living on and off reservations for inclusion in national estimates of diabetes prevalences.
Abstract 4292: <i>In vivo</i> and <i>in vitro</i> imaging of Cyclooxygenase-2 in tumor
Authors: Kenneth Wong, Konnie Urban, Angel Ang, Ning Zhang, Rajendra Singh, Jae-Beom Kim
Journal: Cancer Research (2012)

Abstract Cyclooxygenase-2 (Cox-2) is a biomarker for tumor progression and inflammatory diseases. It is known that normal tissues express minimal amounts of Cox-2 proteins while inflammatory and malignant tumor cells express high levels. Thus, inhibition of Cox-2 is a strategy in the treatment of tumor progression and inflammatory diseases. Recently, many different kinds of molecular imaging reagents for Cox-2 have been developed. Among them, an indomethacin-based Cox-2 probe, fluorocoxib, has been shown to bind to Cox-2 in vitro and in vivo. The binding specificity to Cox-2 was shown using cell culture and tumor xenograph models. In our present study, in order to optimize fluorocoxib imaging conditions, we utilized HCT116 and HT29 cells as low and high Cox-2 expressers, respectively. First, cultured cells were grown overnight on cover slips. Cells were then fixed with paraformaldehyde and incubated with fluorocoxib probe. Multispectral images were taken using a camera equipped with liquid crystal tunable filters. Spectral unmixing was applied to these images to enhance fluorocoxib signals. Our results indicate that HCT116 cells express fair amounts of Cox-2 protein. We also transplanted HCT116 and HT29 cells into the flank regions of nu/nu mice subcutaneously. After tumors grew to sufficient size (∼100 mm3) we injected fluorocoxib intravenously and monitored probe binding to the tumors. Whole animal in vivo imaging indicated that fluorocoxib binds to HT29 tumors after 3 hours. All the probes were eliminated from the animals by 24 hours. On the other hand, HCT116 tumors did not show strong binding of fluorocoxib as expected. However, HCT116 tumors did show some weak binding at the 3 and 6 hr time points. Once there was no longer any probe detected in vivo, we dissected the primary tumors from the HCT116 and HT29 implantations. Tissue sections were made with paraffin embedded tumors. After deparaffinization, tissue sections were incubated with fluorocoxib and fluorescent images were taken using multispectral imaging technology. Spectral unmixing data confirmed that HCT116 tumor sections showed fair amounts of Cox-2 probe expression. The amount of binding was also quantitated using a corresponding software package. Our results demonstrated that fluorescent biomarker probes can be imaged in vitro and in vivo non-invasively. Furthermore, we showed that the expression level can be quantitated using spectral unmixing imaging technology. 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 4292. doi:1538-7445.AM2012-4292