tbuckley/cabot-search huggingface dataset:
Inhibition of the Inflammatory Cytokine TNF-α Increases Adenovirus Activity in Ovarian Cancer via Modulation of cIAP1/2 Expression
Authors: Michael A Salako, Hagen Kulbe, Carin K Ingemarsdotter, Katrina J Pirlo, Sarah L Williams, Michelle Lockley, Frances R Balkwill, Iain A McNeish
Journal: Molecular Therapy (2010)

Oncolytic adenoviruses show promise as a cancer treatment. However, they generate acute inflammatory responses with production of cytokines, including tumor necrosis factor-α (TNF-α). We investigated whether inhibition of TNF-α augments efficacy of the E1A CR2-deleted adenovirus dl922-947 in ovarian cancer. dl922-947 induced transcription of TNF-α and its downstream signaling targets interleukin-6 and -8 (IL-6 and IL-8) in ovarian cancer cells. In vitro, RNAi-mediated knockdown of TNF-α reduced production of multiple inflammatory cytokines after infection and increased ovarian cancer cell sensitivity to virus cytotoxicity, as did treatment with the anti-TNF-α antibody infliximab. In vivo, stable knockdown of TNF-α in IGROV-1 xenografts increased the anticancer activity of dl922-947. In addition, inhibition of TNF-α using monoclonal antibodies also improved dl922-947 efficacy. This increased efficacy resulted from suppression of cellular inhibitor of apoptosis-1 and -2 (cIAP1 and cIAP2) transcription in malignant cells and a consequent increase in caspase-mediated apoptosis. These findings suggest that TNF-α acts as a survival factor in adenovirus-infected cells. Combining TNF-α inhibition with oncolytic adenoviruses could improve antitumor activity in clinical trials.
Still on the Same Slope: Groningen Breaks No New Ethical Ground
Authors: Stephen S. Hanson
Journal: The American Journal of Bioethics (2009)

"Still on the Same Slope: Groningen Breaks No New Ethical Ground." The American Journal of Bioethics, 9(4), pp. 67–68 This Open Peer Commentary addresses Alan Jotkowitz, S. Glick, and B. Gesundheit's Target Article “A Case Against Justified Non-Voluntary Active Euthanasia (The Groningen Protocol)” from The American Journal of Bioethics 8(11): 23–26 and the Open Peer Commentaries that follow on pp. 27–35. Notes 1. See, e.g., the American Academy of Pediatrics 2007, which emphasizes “… treatment decisions that are guided primarily by the best interest of the child” (401). 2. For a further discussion of this understanding of the importance of autonomy and beneficence in informed consent and advance care planning, see Hanson and Doukas, 2009. 3. It is worth noting that they recommend that “ethicists should take into account in our multicultural world” the fact that “many of the world's citizens” believe that there is a morally relevant distinction between killing and letting die. It would seem that the best way to respect this is to make laws that allow persons with different views to exercise those views, rather than being limited to exercising the views of the majority.
The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia.
Authors: A H Lockwood, J M McDonald, R E Reiman, A S Gelbard, J S Laughlin, T E Duffy, F Plum
Journal: Journal of Clinical Investigation (1979)

The cyclotron-produced radionuclide, 13N, was used to label ammonia and to study its metabolism in a group of 5 normal subjects and 17 patients with liver disease, including 5 with portacaval shunts and 11 with encephalopathy. Arterial ammonia levels were 52-264 micron. The rate of ammonia clearance from the vascular compartment (metabolism) was a linear function of its arterial concentration: mumol/min = 4.71 [NH3]a + 3.76, r = +0.85, P less than 0.005. Quantitative body scans showed that 7.4 +/- 0.3% of the isotope was metabolized by the brain. The brain ammonia utilization rate, calculated from brain and blood activities, was a function of the arterial ammonia concentration: mumol/min per whole brain = 0.375 [NH3]a - 3.6, r = +0.93, P less than 0.005. Assuming that cerebral blood flow and brain weights were normal, 47 +/- 3% of the ammonia was extracted from arterial blood during a single pass through the normal brains. Ammonia uptake was greatest in gray matter. The ammonia utilization reaction(s) appears to take place in a compartment, perhaps in astrocytes, that includes less than 20% of all brain ammonia. In the 11 nonencephalopathic subjects the [NH3]a was 100 +/- 8 micron and the brain ammonia utilization rate was 32 +/- 3 mumol/min per whole brain; in the 11 encephalopathic subjects these were respectively elevated to 149 +/- 18 micron (P less than 0.01), and 53 +/- 7 mumol/min per whole brain (P less than 0.01). In normal subjects, approximately equal to 50% of the arterial ammonia was metabolized by skeletal muscle. In patients with portal-systemic shunting, muscle may become the most important organ for ammonia detoxification. Muscle atrophy may thereby contribute to the development of hyperammonemic encephalopathy with an associated increase in the brain ammonia utilization rate.
Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway
Authors: E. G EZRAILSON, H. G HANLEY, C. J HARTLEY, R. M LEWIS, M. L ENTMAN, A. SCHWARTZ
Journal: Cardiovascular Research (1982)

Journal Article Studies on the mechanism of an antibiotic ionophore, R02-2985 (X537A) in the conscious chronically instrumented dog: involvement of the prostaglandin synthetic pathway Get access EDWARD G EZRAILSON, EDWARD G EZRAILSON From the Departments of Medicine and Cell Biophysics, Section of Cardiovascular Sciences, Baylor College of Medicine and the Fondren-Brown Cardiovascular Research and Training Center of The Methodist Hospital, Houston, Texas 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar HENRY G HANLEY, HENRY G HANLEY * From the Departments of Medicine and Cell Biophysics, Section of Cardiovascular Sciences, Baylor College of Medicine and the Fondren-Brown Cardiovascular Research and Training Center of The Methodist Hospital, Houston, Texas 77030 *Present address: Department of Medicine, Louisiana State University School of Medicine, Shreveport, Louisiana, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar CRAIG J HARTLEY, CRAIG J HARTLEY From the Departments of Medicine and Cell Biophysics, Section of Cardiovascular Sciences, Baylor College of Medicine and the Fondren-Brown Cardiovascular Research and Training Center of The Methodist Hospital, Houston, Texas 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBERT M LEWIS, ROBERT M LEWIS From the Departments of Medicine and Cell Biophysics, Section of Cardiovascular Sciences, Baylor College of Medicine and the Fondren-Brown Cardiovascular Research and Training Center of The Methodist Hospital, Houston, Texas 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar MARK L ENTMAN, MARK L ENTMAN From the Departments of Medicine and Cell Biophysics, Section of Cardiovascular Sciences, Baylor College of Medicine and the Fondren-Brown Cardiovascular Research and Training Center of The Methodist Hospital, Houston, Texas 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar ARNOLD SCHWARTZ ARNOLD SCHWARTZ From the Departments of Medicine and Cell Biophysics, Section of Cardiovascular Sciences, Baylor College of Medicine and the Fondren-Brown Cardiovascular Research and Training Center of The Methodist Hospital, Houston, Texas 77030 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 11, November 1982, Pages 670–674, https://doi.org/10.1093/cvr/16.11.670 Published: 01 November 1982
THE CORONER SYSTEM IN THE UNITED STATES.Read in the Section of State Medicine, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, V. C, May, 1891.
Authors: HENRY O. MARCY
Journal: JAMA (1891)

I am aware that the great body of the medical profession have regarded the coroner and his duties as a subject bearing only an indirect rela- tion to the practice of medicine.It was not until 1877, when the coroner laws were pretty thor- oughly investigated in Massachusetts, that I be- lieved they demanded revision.The investigation of the law as practiced in Massachusetts showed clearly that it was not adapted to the best ends of justice ; that the cor- oner, no matter how skilled in any branch of special training, could, under the law, scarcely be expected to discharge his duties in a satisfac- tory manner.In other words, that the primal fault lay, not so much in the functionary as in the class of duties he was expected to fulfill.The analysis of these duties showed that the same person was expected to be competent as a medical expert, to serve as an administrator of the law, as a judge to hear evidence, to decide upon its admissibility, he being also a witness in the case.Upon his own authority, or assisted by a physician, he was first to determine in a case under investigation if death had occurred by natural means or by violence ; that is, by the evil intent of another.It having been decided that further investigation was necessary, a jury was summoned, and testimony was taken, usually in open session.To this he added his own tes¬ timony.From this brief review it will be clearly ob¬
Detection of a Mammographically Occult Invasive Lobular Breast Carcinoma by PET/CT in a Patient With Lymphoma
Authors: Daria E. Setlik, Judith M. Joyce, Samuel A. Jacobs
Journal: Clinical Nuclear Medicine (2009)

We present a case of invasive lobular breast carcinoma which was detected incidentally by positron emission tomography/computed tomography (PET/CT) in a patient with lymphoma, although occult on the subsequent mammogram. This 60-year-old female, with a history of non-Hodgkin lymphoma, underwent PET/CT imaging for routine follow-up which demonstrated a new hypermetabolic focus in the right breast suspicious for malignancy. Further workup showed no mammographic abnormality, but ultrasound-guided biopsy demonstrated this to be an unsuspected primary breast carcinoma. This case indicates that evaluation of the breasts is important to include in PET/CT interpretation, and abnormalities should be diligently pursued despite lack of mammographic correlation.
Abstract LB-17: Oral delivery of taurocholic acid-linked heparin-docetaxel conjugates for tumor and its angiogenesis therapy
Authors: Zehedina Khatun, MD Nurunnabi, Kang Moo Huh, Yong-kyu Lee
Journal: Cancer Research (2014)

Abstract Oral delivery is the preferred route to deliver therapeutics via nanoparticles due to ease of administration and patient acceptance. Here, we report on the findings of the absorption pathway of taurocholic acid (TCA)-linked heparin and docetaxel (DTX) conjugate, which we refer to as HDTA. The ternary biomolecular conjugates formed self-assembly nanoparticles where docetaxel was located inside the core and taurocholic acid was located on the surface of the nanoparticles. The oral absorption profile demonstrated that the concentration of the conjugates in plasma is about 6 fold higher than heparin alone. An anti-tumor study in MDA-MB231 and KB tumor bearing mice showed significant tumor growth inhibition activity by the ternary biomolecular conjugates. We studied the oral absorption of HDTA using a Caco-2 cell transport system and an animal model. We have also used other absorption enhancers, such as ethylene glycol tetraacetic acid (EGTA), or inhibitors, such as sodium azide, to compare the relative permeability of HDTA conjugates. In vivo comparative studies were conducted using free TCA as a pre-administration and exhibited the maximum absorption site of the organ after oral administration of HDTA conjugates. HDTA was found to be absorbed mainly in the ileum and Caco-2 cell monolayer through passive diffusion and bile acid transporters. High fluorescence intensity of HDTA in mice came from the ileum, and it was eliminated from the body through colon. This novel formulation could be further investigated by clinical trials to find the prospect of oral anti-cancer drug delivery through anti-angiogenic treatment strategies. Citation Format: Zehedina Khatun, MD Nurunnabi, Kang Moo Huh, Yong-kyu Lee. Oral delivery of taurocholic acid-linked heparin-docetaxel conjugates for tumor and its angiogenesis therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-17. doi:10.1158/1538-7445.AM2014-LB-17
Reduction of Restenosis After Angioplasty in an Atheromatous Rabbit Model by Suicide Gene Therapy
Authors: P. Gabriel Steg, Ouafae Tahlil, Nathalie Aubailly, Jean-Michel Caillaud, Jean-François Dedieu, Karine Berthelot, Aude Le Roux, Laurent Feldman, Michel Perricaudet, Patrice Denèfle, Didier Branellec
Journal: Circulation (1997)

Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis.A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5, P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury.In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.
More trials on early treatment with corticosteroids are needed
Authors: N V Subhedar
Journal: BMJ (2000)

EDITOR—We agree with the sentiments expressed by Tarnow-Mordi and Mitra in their editorial—namely, that randomised controlled trials with longer term follow up are required to answer the question of how corticosteroids affect long term outcome in preterm babies.1

We have followed up 42 preterm infants enrolled into a randomised controlled trial of early dexamethasone to prevent chronic lung disease.2 Seventeen died before discharge, and a further three died after discharge from hospital. A detailed assessment was performed in 21 of the 22 survivors (one infant lost to follow up) at 30 months of age, corrected for prematurity, with the assessor …
[96] CLUSTERING OF CDS T CELL RESPONSES AGAINST THE HBV CORE AND SURFACE PROTEINS WITHIN DIFFERENT HLA ALLELES: IMMUNODOMINANCE ANALYSIS IN PATIENTS WITH DIVERSE GENETIC BACKGROUNDS
Authors: F. Bihl, E. Loggi, J.V. Chisholm III, C. Fortini, M. Margotti, K. Faircloth, C. Cursaro, M. Bernard, P. Andreone, C. Brander
Journal: Journal of Hepatology (2007)
HCV glycoprotein E2 is a novel BDCA-2 ligand and acts as an inhibitor of IFN production by plasmacytoid dendritic cells
Authors: Jonathan Florentin, Besma Aouar, Clélia Dental, Christine Thumann, Guylène Firaguay, Francoise Gondois-Rey, Vassili Soumelis, Thomas F. Baumert, Jacques A. Nunès, Daniel Olive, Ivan Hirsch, Ruzena Stranska
Journal: Blood (2012)
Comparison of single-breath and plethysmographic measurements of resistance in infancy.
Authors: I Dundas, C A Dezateux, M E Fletcher, E A Jackson, J Stocks
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Single-breath technique (SBT) measurements of total respiratory resistance (Rrs) were compared with plethysmographic measurements of airway resistance (Raw) in healthy infants < or = 13 wk of age (Group 1; n = 49) and > 13 wk of age (Group 2; n = 37) and in infants > 13 wk of age with prior wheeze (Group 3; n = 49). A significantly higher percentage of Rrs (19%) than of Raw (2%) measurements were technically unsatisfactory, alinearity of the flow-volume curve accounting for 54% of Rrs failures. Although both Rrs and Raw were significantly higher in Group 3 infants, between-subject variability was wide in all groups. Rrs was significantly higher than initial expiratory (IE) Raw in all groups. Mean difference Rrs-IE Raw (95% CI) values were 1.98 (1.51, 2.48), 1.29 (0.96, 1.62), and 1.97 (1.56, 2.38) kPa.L-1.s for Groups 1, 2, and 3, respectively. Significant but smaller differences were seen for end-expiratory (EE) Raw in Groups 1 and 2 but not in Group 3. Mean difference Rrs-EE Raw (95% CI) values were 0.68 (0.11, 1.26), 0.55 (0.19, 0.92), and 0.31 (-0.06, 0.69) kPa.L-1.s for Groups 1, 2, and 3, respectively. Despite wide between-subject variability in Rrs and a relatively high failure rate, the SBT is simple to use, and it may be applicable to epidemiologic studies. However, clinical applications in individual infants may be limited by failure to detect the dynamic changes in resistance throughout the breath evident from plethysmographic studies.
Immunization to Prevent Insulin-Dependent Diabetes Mellitus?
Authors: WILLIAM L. ENGLAND
Journal: Annals of Internal Medicine (1981)

There is increasing evidence that some cases of insulindependent diabetes mellitus are virally induced, and vaccination against this disease may become possible. We have prospectively examined the costs and benefits that would occur if a diabetes vaccine were developed, using a decision tree to model the alternative vaccination policies, including histocompatibility leukocyte antigen (HLA) screening. We found many cost and likelihood data in the literature, and when data on the potential vaccine had to be hypothesized, we used sensitivity analysis to check our estimates. We conclude that vaccinating all children at age 3 would be preferable to HLA screening and vaccinating only persons with a genetic predisposition to developing diabetes. A 50% effective vaccine would cut the diabetes incidence rate by 29% and save the U.S. population $30 million annually in direct costs of diabetes care. If indirect costs are considered these savings could amount to $4.2 billion over 60 years, discounted to present value at 5%, while preventing over 200 000 cases of insulin-dependent diabetes.
Role of the hepatic artery in canalicular bile formation by the perfused rat liver. A multiple indicator dilution study.
Authors: J Reichen
Journal: Journal of Clinical Investigation (1988)

The role of the hepatic artery in tracer water exchange and regulation of permeation of small solutes during canalicular bile formation was studied in the rat using a system that permitted perfusion of both hepatic artery and portal vein. Hepatic vein and biliary multiple indicator dilution curves were obtained after injection of indicators into either vessel. The main difference in hepatic venous dilution curves was a 3.1-fold longer t0 (time spent in nonexchanging vessels) and a 5% larger equivalent water space after injection into the hepatic artery. Biliary tracer recovery of water was markedly higher after arterial injection than after portal vein injection. Both taurocholate and taurodehydrocholate stimulated bile flow and increased biliary tracer recovery after injection into either vessel. The biliary recovery of sucrose relative to that of water, which is a measure of biliary sucrose permeation, was much lower when given into the hepatic artery than when given into the portal vein. During taurocholate infusion, it decreased by 33% in the hepatic artery but increased 36% in the portal vein. Taurodehydrocholate, by contrast, did not affect permeation of sucrose given into the portal vein. Our studies demonstrate marked exchange of tracer water in the biliary epithelium. Taurocholate, but not taurodehydrocholate, increases permeation of sucrose into bile in the portal vein bed while both bile salts decrease it in the arterial bed.
Protease-cleaved iron-transferrin augments oxidant-mediated endothelial cell injury via hydroxyl radical formation.
Authors: R A Miller, B E Britigan
Journal: Journal of Clinical Investigation (1995)

Previous work has shown that the Pseudomonas-derived protease, pseudomonas elastase (PAE), can modify transferrin to form iron complexes capable of catalyzing the formation of hydroxyl radical (.OH) from neutrophil (PMN)-derived superoxide (.O2-) and hydrogen peroxide (H2O2). As the lung is a major site of Pseudomonas infection, the ability of these iron chelates to augment oxidant-mediated pulmonary artery endothelial cell injury via release of 51Cr from prelabeled cells was examined. Diferrictransferrin previously cleaved with PAE significantly enhanced porcine pulmonary artery endothelial cell monolayer injury from 2.3-6.3 to 15.8-17.0% of maximum, resulting from exposure to H2O2, products of the xanthine/xanthine oxidase reaction, or PMA-stimulated PMNs. Iron associated with transferrin appeared to be responsible for cell injury. Spin trapping and the formation of thiobarbituric acid-reactive 2-deoxyribose oxidation products demonstrated the production of .OH in this system. The addition of catalase, dimethyl thiourea, and the hydrophobic spin trap, alpha-phenyl-n-terbutyl-nitrone, offered significant protection from injury (27.8-58.2%). Since sites of Pseudomonas infection contain other proteases, the ability of porcine pancreatic elastase and trypsin to substitute for PAE was examined. Results were similar to those observed with PAE. We conclude .OH formation resulting from protease alteration of transferrin may serve as a mechanism of tissue injury at sites of bacterial infection and other processes characterized by increased proteolytic activity.
TARDY MALNUTRITION: ITS TREATMENT BY DIET AND REST.
Authors: CHARLES G. KERLEY
Journal: JAMA (1907)

tage of being about 1,300 years earlier than this, and is, besides, unmutilated.The person or persons cir- cumcised in this representation are not boys of from 6 to S years, as in the other picture that we have just mentioned, but young men, so that, as Mr. Miil- ler says, it is clear that the earliest custom in Egypt in this matter was perfectly in harmony with the earlier Semitic usage.Circumcisions seem, therefore, to have preceded marriage only by a comparatively short time.According to Miiller, this is known to have been the case with regard to females from a papyrus of the Greek period in the British Museum, and it is now seen to have been the custom also for males.
Wonton, Straight Up
Authors: Alexander Leung
Journal: JAMA (1985)

<h3>To the Editor.—</h3> In a recent letter inThe Journal<sup>1</sup>Dr John Cochran and his wife Arlene described their 3-year-old daughter who, on three separate occasions, developed 30- to 45-minute episodes of inappropriate behavior, confusion, and slight ataxia of gait after she had eaten wonton soup along with cola. "She was not unlike an adult mildly intoxicated with alcohol." I did a random study of 100 Chilnese families and was surprised to find out that 28% of them added wine to the food during the cooking process. This figure might be higher in Chinese restaurants. Although monosodium glutamate (MSG) is most probably the cause of Chinese restaurant syndrome, the role played by alcohol should not be ignored.
Alpha1a-adrenergic receptor polymorphism influences baroreflex sensitivity and nonsustained ventricular tachycardia in idiopathic dilated cardiomyopathy
Authors: Cinzia Forleo, Pietro Guida, Sandro Sorrentino, Massimo Iacoviello, Viviana De Luca, Roberta Romito, Federica Troisi, Andrea Manghisi, Paolo Rizzon, Mariavittroia Pitzalis
Journal: Journal of the American College of Cardiology (2003)