tbuckley/cabot-search huggingface dataset:
Enhancement of Angiogenesis Through Stabilization of Hypoxia-inducible Factor-1 by Silencing Prolyl Hydroxylase Domain-2 Gene
Authors: Shourong Wu, Nobuhiro Nishiyama, Mitsunobu R Kano, Yasuyuki Morishita, Kohei Miyazono, Keiji Itaka, Ung-il Chung, Kazunori Kataoka
Journal: Molecular Therapy (2008)

Hypoxia-inducible factor-1 (HIF-1) plays a central role in cellular response to hypoxia by activating vascular endothelial growth factor (VEGF) and other angiogenic factors. Prolyl hydroxylase domain-2 (PHD2) protein induces the degradation of HIF-1 by hydroxylating specific prolyl residues. Therefore gene silencing of PHD2 by RNA interference (RNAi) might increase the expression of angiogenic growth factors and, consequently, neoangiogenesis through the stabilization of HIF-1alpha. In this study we have shown that the specific silencing of PHD2 is sufficient for stabilizing HIF-1alpha and increasing its transcriptional activity, resulting in the increased expression of angiogenic factors including VEGF and fibroblast growth factor-2 (FGF2). Moreover, when PHD2-siRNA vector was used, the increase in VEGF secretion was observed for as long as 18 days after transfection. In vitro treatment of human umbilical vein endothelical cells with conditioned medium from PHD2-siRNA vector-transfected NIH3T3 cells was shown to increase cell proliferation. Also, in vivo angiogenesis was observed in mice implanted with Matrigel plugs mixed with NIH3T3 cells transfected with PHD2-siRNA vector. These results indicate that PHD2 silencing induces expressions of multiple angiogenic growth factors by stabilizing HIF-1alpha, and that the implantation of cells transfected with PHD2-siRNA vector is sufficient to enhance angiogenesis in vivo. In the light of these findings, PHD2 silencing by RNAi might offer a potential tool for angiogenic therapy.
Clinical and Economic Outcomes of Liberal Versus Selective Drug-Eluting Stent Use
Authors: Lakshmi Venkitachalam, Yang Lei, Joshua M. Stolker, Elizabeth M. Mahoney, Amit P. Amin, Jason B. Lindsey, Kevin F. Kennedy, Michael J. Pencina, John J. Lopez, Neal S. Kleiman, David J. Cohen
Journal: Circulation (2011)

Although the benefits of drug-eluting stents (DES) for reducing restenosis after percutaneous coronary intervention are well established, the impact of alternative rates of DES use on population-level outcomes is unknown.We used data from the Evaluation of Drug Eluting Stents and Ischemic Events (EVENT) registry to examine the clinical impact and cost-effectiveness of varying DES use rates in routine care. Between 2004 and 2007, 10,144 patients undergoing percutaneous coronary intervention were enrolled in the EVENT registry at 55 US centers. Clinical outcomes and cardiovascular-specific costs were assessed prospectively over 1 year of follow-up. Use of DES decreased from 92 in 2004 to 2006 (liberal use era; n=7587) to 68 in 2007 (selective use era; n=2557; P<0.001). One-year rates of death or myocardial infarction were similar in both eras. Over this time period, the incidence of target lesion revascularization increased from 4.1 to 5.1, an absolute increase of 1.0 (95 confidence interval, 0.1 to 1.9; P=0.03), whereas total cardiovascular costs per patient decreased by $401 (95 confidence interval, 131 to 671; P=0.004). The risk-adjusted incremental cost-effectiveness ratio for the liberal versus selective DES era was $16,000 per target lesion revascularization event avoided, $27,000 per repeat revascularization avoided, and $433 000 per quality-adjusted life-year gained.In this prospective registry, a temporal reduction in DES use was associated with a small increase in target lesion revascularization and a modest reduction in total cardiovascular costs. These findings suggest that although clinical outcomes are marginally better with unrestricted DES use, this approach represents a relatively inefficient use of healthcare resources relative to several common benchmarks for cost-effective care.
Chloride dependence of pH modulation by beta-adrenergic agonist in rat cardiomyocytes.
Authors: M Désilets, M Pucéat, G Vassort
Journal: Circulation Research (1994)

The effects of beta-adrenergic agonists on pHi were studied on single ventricular myocytes isolated from adult rat heart and loaded with the acetoxymethyl ester (AM) form of the pH indicator SNARF-1. In modified Krebs' solution containing 20 mmol/L HEPES and 4.4 mmol/L HCO3-, isoproterenol (1 mumol/L) caused a significant decrease of steady-state pHi from 7.20 +/- 0.02 to 7.13 +/- 0.02 (mean +/- SEM) within 2 minutes. This acidification, which was also observed in myocytes that were preloaded with the Ca2+ chelator BAPTA and superfused with nominally Ca(2+)-free solution, was blocked by propranolol as well as by the specific beta 1-antagonist CGP 20712 A but not by the beta 2-antagonist ICI 118,551. Forskolin (10 mumol/L) induced a similar reversible decrease of pHi (average decrease, 0.11 +/- 0.02 pH unit). Furthermore, adenosine (100 mumol/L) substantially attenuated the isoproterenol-induced decrease of pHi. The effect of isoproterenol was not prevented by inhibitors of the Na(+)-H+ antiport, amiloride (1 mmol/L) and 2-N,N-hexamethylene amiloride (20 mumol/L). On the other hand, blockers of Cl- transport mechanisms, DIDS (200 mumol/L) and probenecid (100 mumol/L), inhibited this acidification, Isoproterenol also failed to induce a decrease of steady-state pHi in myocytes incubated in Cl(-)-free medium. Rather, the initial rate of rise of pHi observed on removal of external Cl- ions was significantly increased in the presence of isoproterenol or dibutyryl cAMP. Because the alkalinization induced by removal of Cl- ions is mainly due to reversal of the Cl(-)-HCO3- exchanger, the augmentation of this initial rate of pHi rise directly points to a beta-adrenergic stimulation of the exchanger. Furthermore, the pHi recovery following NH4Cl exposure was accelerated by isoproterenol in the presence of probenecid, indicating that the Na(+)-HCO3- cotransport and/or the Na(+)-H+ antiport also could be activated.(ABSTRACT TRUNCATED AT 250 WORDS)
The Injuries to JFK-Reply
Authors: J. Thornton Boswell
Journal: JAMA (1992)

<h3>In Reply.</h3> —The appearance and location of the President's wounds were exactly as described in the original autopsy report. That report was prepared within 48 hours of the assassination and delivered to the White House physician early in the evening of November 24,1963. No amount of discussion or debate can alter these facts. We concur with the recommendations that all of the material related to this tragedy should be made available to qualified individuals. We continue to believe that no useful purpose would be served by widespread publication of the very unsightly head wounds and we lament the fact that this has already, to some extent, occurred.
Radon—Getting the Dosimetry Right
Authors: James E. Watson
Journal: JAMA (1988)

<h3>To the Editor.—</h3> We have recently, and, we admit, belatedly, discovered some serious errors in the radiation doses reported for exposure to indoor radon and its progeny in the report of the Council on Scientific Affairs<sup>1</sup>on radon in homes. The report states that "exposure of the lungs to a level of 1.3 pCi/L (0.048 Bq/L)... would result in an annual radiation dose of 8.7 mrem," referencing Sorenson.<sup>2</sup>Sorenson's article, however, shows that a concentration of 1300 pCi/m<sup>3</sup>(equivalent to 1.3 pCi/L) results in an annual dose of 8700 mrem, or 8.7 rem! A reader might well wonder what all the fuss was about if, in fact, exposure to an average level of radon resulted in a dose somewhat less than that from a single chest roentgenogram. The offending paragraph was not in the version of the report one of us (R.E.T.) reviewed prior to publication. We were
Toward a Science of Brain Death
Authors: Andrew Peterson, Loretta Norton, Lorina Naci, Adrian M. Owen, Charles Weijer
Journal: The American Journal of Bioethics (2014)

Click to increase image sizeClick to decrease image size ACKNOWLEDGMENTSWe thank Anthony Belardo for editorial assistance. A. Peterson is supported by a Vanier Canada Graduate Scholarship. A. M. Owen holds the Canada Excellence Research Chair in Cognitive Neuroscience and Imaging. C. Weijer holds the Canada Research Chair in Bioethics.
Perinatal Exposure to Low Doses of Dioxin Can Permanently Impair Human Semen Quality
Authors: Paolo Mocarelli, Pier Mario Gerthoux, Larry L. Needham, Donald G. Patterson, Giuseppe Limonta, Rosanna Falbo, Stefano Signorini, Maria Bertona, Carla Crespi, Cecilia Sarto, Paul K. Scott, Wayman E. Turner, Paolo Brambilla
Journal: Environmental Health Perspectives (2011)

In recent decades, young men in some industrialized areas have reportedly experienced a decrease in semen quality.We examined effects of perinatal dioxin exposure on sperm quality and reproductive hormones.We investigated sperm quality and hormone concentrations in 39 sons (mean age, 22.5 years) born between 1977 and 1984 to mothers exposed to dioxin after the accident in Seveso, Italy (1976), and 58 comparisons (mean age, 24.6 years) born to mothers exposed only to background dioxin. Maternal dioxin levels at conception were extrapolated from the concentrations measured in 1976 serum samples.The 21 breast-fed sons whose exposed mothers had a median serum dioxin concentration as low as 19 ppt at conception had lower sperm concentration (36.3 vs. 86.3 million/mL; p = 0.002), total count (116.9 vs. 231.1; p = 0.02), progressive motility (35.8 vs. 44.2%; p = 0.03), and total motile count (38.7 vs. 98 million; p = 0.01) than did the 36 breast-fed comparisons. The 18 formula-fed exposed and the 22 formula-fed and 36 breast-fed comparisons (maternal dioxin background 10 ppt at conception) had no sperm-related differences. Follicle-stimulating hormone was higher in the breast-fed exposed group than in the breast-fed comparisons (4.1 vs. 2.63 IU/L; p = 0.03) or the formula-fed exposed (4.1 vs. 2.6 IU/L; p = 0.04), and inhibin B was lower (breast-fed exposed group, 70.2; breast-fed comparisons, 101.8 pg/mL, p = 0.01; formula-fed exposed, 99.9 pg/mL, p = 0.02).In utero and lactational exposure of children to relatively low dioxin doses can permanently reduce sperm quality.
Women who have prophylactic mastectomy overstate risk of cancer
Authors: D. Spurgeon
Journal: BMJ (2002)

Women who undergo prophylactic bilateral mastectomy have an exaggerated perception of their risk of breast cancer before the surgery, concludes a Canadian study. Before deciding on the procedure women should be strongly encouraged to seek genetic counselling and genetic testing, it recommends ( Journal of the National Cancer Institute 2002;94:1564-9)

The study, which involved 75 women in Ontario who had had the operation between 1991 and 2000, found that most of them overestimated their risk of developing breast cancer by more than 90% compared with computer generated risks based on epidemiological observations.

University of …
Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation
Authors: André Tichelli, Christoph Bucher, Alicia Rovó, Georg Stussi, Martin Stern, Michael Paulussen, Jörg Halter, Sandrine Meyer-Monard, Dominik Heim, Dimitrios A. Tsakiris, Barbara Biedermann, Jakob R. Passweg, Alois Gratwohl
Journal: Blood (2007)
Leukocyte-platelet interaction. Release of hydrogen peroxide by granulocytes as a modulator of platelet reactions.
Authors: P H Levine, R S Weinger, J Simon, K L Scoon, N I Krinsky
Journal: Journal of Clinical Investigation (1976)

Because of the many potent biological capabilities of the blood granulocytes, and their contact with platelets in various physiologic and pathologic states, a possible interaction between granulocytes and platelets was investigated. Platelets were purified by gel filtration and via a dialysis membrane were separated from suspensions of autologous granulocytes prepared by dextran sedimentation and resuspended in modified Tyrode's buffer. After 20 min at 37 degrees C platelet aggregation was shown to be diminished by such exposure, as compared to the aggregation of platelets incubated with dialysates of buffer only. When granulocytes were stimulated by the addition of 1.1-muM latex spheres as target particles for phagocytes, the dialysate of these cells exhibited greatly enhanced platelet-inhibitory properties. The addition of catalase to the platelets abolished the effect of exposing these cells to the dialysate of resting granulocytes and markedly inhibited the effect of exposing the platelets to the dialysate of phagocytosing granulocytes. Catalase treated with 3-amino-1,2,4-triazole had no platelet-protective capacity. Purified suspensions of lymphocytes released no platelet-inhibitory principle under these experimental conditions. Hydrogen peroxide in the dialysate of granulocytes was measured directly with an assay involving an H2O2-induced decrease in the fluorescence of scopoletin catalyzed by horseradish peroxidase. The dialysate of phagocytosing granulocytes contained 0.86 +/- 0.55 nmol H2O2/2.5 X 10(7) granulocytes when sampled at 20 min. By an alternate measurement technique in which scopoletin and horseradish peroxidase were present in the dialysate from time zero, the mean amount of H2O2 in the dialysate reached 4.0 +/- 1.3 nmol/2.5 x 10(7) granulocytes at 20 min. This discrepancy suggested the consumption of H2O2, possibly mediated by the granulocytes themselves. This possibility was investigated by the addition of exogenous H2O2 to the test system. Both granulocytes and platelets enhanced the disappearance of H2O2 from the dialysate, and the amount consumed was proportional to the amount of H2O2 added to the system. Glucose oxidase at 12 M U/ml plus glucose in excess resulted in the production of H2O2 at a rate and final amount comparable to that produced by phagocytosing granulocytes. This mixture, when substituted for phagocytosing granulocytes in the standard dialysis membrane experiment, induced an inhibition of platelet aggregation similar to that caused by the granulocytes. The observation that the release of H2O2 by the blood granulocyte influences platelet function suggests a potential role for the granulocyte in the regulation of hemostasis or thrombosis.
Obstructive uropathy in the mouse: Role of osteopontin in interstitial fibrosis and apoptosis
Authors: Vuddhidej Ophascharoensuk, Cecilia M. Giachelli, Katherine Gordon, Jeremy Hughes, Raimund Pichler, Paul Brown, Lucy Liaw, Rodney Schmidt, Stuart J. Shankland, Charles E. Alpers, William G. Couser, Richard J. Johnson
Journal: Kidney International (1999)
Associations between palliative chemotherapy and adult cancer patients' end of life care and place of death: prospective cohort study
Authors: A. A. Wright, B. Zhang, N. L. Keating, J. C. Weeks, H. G. Prigerson
Journal: BMJ (2014)

<b>Objectives</b> To determine whether the receipt of chemotherapy among terminally ill cancer patients months before death was associated with patients' subsequent intensive medical care and place of death. <b>Design</b> Secondary analysis of a prospective, multi-institution, longitudinal study of patients with advanced cancer. <b>Setting</b> Eight outpatient oncology clinics in the United States. <b>Participants</b> 386 adult patients with metastatic cancers refractory to at least one chemotherapy regimen, whom physicians identified as terminally ill at study enrollment and who subsequently died. <b>Main outcome measures</b> Primary outcomes: intensive medical care (cardiopulmonary resuscitation, mechanical ventilation, or both) in the last week of life and patients' place of death (for example, intensive care unit). Secondary outcomes: survival, late hospice referrals (≤1 week before death), and dying in preferred place of death. <b>Results</b> 216 (56%) of 386 terminally ill cancer patients were receiving palliative chemotherapy at study enrollment, a median of 4.0 months before death. After propensity score weighted adjustment, use of chemotherapy at enrollment was associated with higher rates of cardiopulmonary resuscitation, mechanical ventilation, or both in the last week of life (14% <i>v</i> 2%; adjusted risk difference 10.5%, 95% confidence interval 5.0% to 15.5%) and late hospice referrals (54% <i>v</i> 37%; 13.6%, 3.6% to 23.6%) but no difference in survival (hazard ratio 1.11, 95% confidence interval 0.90 to 1.38). Patients receiving palliative chemotherapy were more likely to die in an intensive care unit (11% <i>v</i> 2%; adjusted risk difference 6.1%, 1.1% to 11.1%) and less likely to die at home (47% <i>v</i> 66%; −10.8%, −1.0% to −20.6%), compared with those who were not. Patients receiving palliative chemotherapy were also less likely to die in their preferred place, compared with those who were not (65% <i>v</i> 80%; adjusted risk difference −9.4%, −0.8% to −18.1%). <b>Conclusions</b> The use of chemotherapy in terminally ill cancer patients in the last months of life was associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation or both and of dying in an intensive care unit. Future research should determine the mechanisms by which palliative chemotherapy affects end of life outcomes and patients' attainment of their goals.
Exploitation of gamma delta T cells in cancer immunotherapy as combined antigen-presenters and cancer cell killers
Authors: Gitte Holmen Olofsson, Manja Idorn, Wajid Khan, Mads Hald Andersen, Bernhard Moser, Per thor Straten
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The human Vγ9Vδ2 T cells are a unique T cell type, and recent studies of the biology of Vγ9Vδ2 T cells emphasize the potential exploitation of these cells in immunotherapy of cancer. Vγ9Vδ2 T cells exhibit dual functionality in that they are both antigen-presenting cells and
Procaine in Malignant Hyperpyrexia
Authors: R. F. W. Moulds, M. A. Denborough
Journal: BMJ (1972)

The caffeine contracture of normal human muscle, which has been used as a model for malignant hyperpyrexia, is greatly potentiated by halothane. Prior administration of procaine markedly reduces the halothane-potentiated caffeine contracture, and procaine given at the height of the contracture induces relaxation. Lignocaine, on the other hand, produces a variable response and sometimes increases the contracture. The muscle from a patient with an inherited susceptibility to malignant hyperpyrexia contracted spontaneously with halothane alone, and this contracture was reversed by procaine. These experiments support the therapeutic use of procaine in malignant hyperpyrexia.
Resolution of Non–Small-Cell Lung Cancer after Withdrawal of Anti-TNF Therapy
Authors: Charles W. Lees, Janet Ironside, William A.H. Wallace, Jack Satsangi
Journal: New England Journal of Medicine (2008)

To the Editor: We report the development of locally advanced non–small-cell lung cancer (tumor–node–metastasis [TNM] stage T4N2M0) in a 69-year-old woman with Crohn's colitis. Her condition had been diagnosed in 2000 and had required treatment with methotrexate (from 2003 to the present), together with anti–tumor necrosis factor (TNF) therapies — initially, episodic infliximab (from 2000 to 2004) and thereafter, maintenance adalimumab, until the tumor was diagnosed in June 2006. Remarkably, the tumor expressed TNF receptors and underwent regression and sustained remission on withdrawal of anti-TNF therapy, with no other therapeutic intervention. In 1999, the patient, a former smoker (35 pack-years), . . .
Comparative clinical and angiographic findings in patients with symptomatic and asymptomatic restenosis following angioplasty
Authors: George Vetrovec, Germano DiSciascio, Ralph Hugo, John Hirshfeld, Robert MacDonald, Theodore Bass, Sheldon Goldberg, Michael Savage, Elliott Barnathan, Michael Cowley, Hal Whitworth, Andrew Taussig, James Margolis, Carl Pepine
Journal: Journal of the American College of Cardiology (1990)
Heat Exchanger for Profound Hypothermia
Authors: M. Vasulin, O. Oslejsek
Journal: Thorax (1965)

<h3>Abstract</h3> Cold-shock DEAD-box protein A (CsdA) is an ATP dependant cold shock DEAD-box RNA helicase. It is a major cold shock protein needed for the cold adaptation in <i>Escherichia coli</i>. Although the CsdA has been studied at the protein level, further studies are necessary to understand its mechanisms of gene regulations. In this regard, we have constructed a promoter less vector with the ORF of a GFP reporter and found that the promoter of the <i>csdA</i> gene resides far upstream (more than 800 bases) of its coding region. Furthermore, our <i>in vivo</i> deletion experiment has confirmed the existence of this extraordinarily long 5’UTR. Our results show that it represses its own expression. In addition, the short peptide encoding (26 aa) <i>yrbN</i> gene resides within this 5’UTR as an operon with 8 overlapping nucleotides with the <i>csdA</i> coding region. Besides, we observed that the <i>csdA</i> gene expression may also occur along with immediate upstream (180 nucleotides) <i>nlpI</i> gene both at 37°C and 15°C and from the <i>pnp</i> gene (1173 nucleotides upstream) only during cold. In conclusion, <i>csdA</i> gene has operon feature like prokaryotes, in contrast, it also contains an extraordinarily long 5’UTR, found in eukaryotes.