tbuckley/cabot-search huggingface dataset:
Oxygen-free radical-mediated injury to cultured rat hepatocytes during cold incubation in preservation solutions
Authors: U Rauen, I Reuters, A Fuchs, H de Groot
Journal: Hepatology (1997)

We have previously shown that the injury to cultured liver endothelial cells during cold incubation in University of Wisconsin (UW) solution is energy-dependent and is mediated by reactive oxygen species. Here we demonstrate that this reactive oxygen-mediated injury is specific neither to endothelial cells nor to UW solution: cultured hepatocytes incubated in cold (4 degrees C) UW solution or histidine-tryptophan-ketoglutarate (HTK) solution were injured under normoxic conditions (loss of viability, 63% +/- 10% after 48 hours of cold incubation in UW solution and 82% +/- 11% after 24 hours of cold incubation in HTK solution), whereas hypoxia was protective (loss of viability, 29% +/- 12% [UW] and 13% +/- 3% [HTK] after the same cold incubation times). The injury under normoxic conditions was also largely decreased by adding either the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) or the flavonoid silibinin to the solutions, or by preincubating the cells with the iron chelator deferoxamine before the hypothermic incubation. Marked lipid peroxidation was observed during cold incubation in both preservation solutions. These results suggest that the injury to cultured hepatocytes during cold incubation in UW and HTK solutions is mediated by reactive oxygen species as is the injury to cultured liver endothelial cells.
Functionally and Structurally Distinct NK Cell Receptor Repertoires in the Peripheral Blood of Two Human Donors
Authors: Nicholas M Valiante, Markus Uhrberg, Heather G Shilling, Kristin Lienert-Weidenbach, Kelly L Arnett, Annalisa D'Andrea, Joseph H Phillips, Lewis L Lanier, Peter Parham
Journal: Immunity (1997)

The expression of KIR and CD94:NKG2 receptors was determined for more than 100 natural killer (NK) cell clones obtained from two blood donors who differ in their HLA class I and KIR genes. More than 98% of the clones were inhibited by individual autologous class I allotypes, and every clone was inhibited by the combination of autologous allotypes. The patterns of inhibition correlate with expression of inhibitory receptors of defined specificity. One donor possesses three class I ligands for KIR, and a majority of NK cells use KIR as their inhibitory receptor; the second donor possesses only a single ligand for KIR, and a majority of NK cells use the more broadly reactive CD94:NKG2a as their inhibitory receptor. Because of these differences, the first donor has subpopulations of NK cells that kill cells of the second donor, whereas the NK cells of the second donor are universally tolerant of cells from the first donor.
Menin determines K-RAS proliferative outputs in endocrine cells
Authors: Chester E. Chamberlain, David W. Scheel, Kathleen McGlynn, Hail Kim, Takeshi Miyatsuka, Juehu Wang, Vinh Nguyen, Shuhong Zhao, Anastasia Mavropoulos, Aswin G. Abraham, Eric O’Neill, Gregory M. Ku, Melanie H. Cobb, Gail R. Martin, Michael S. German
Journal: Journal of Clinical Investigation (2014)

Endocrine cell proliferation fluctuates dramatically in response to signals that communicate hormone demand. The genetic alterations that override these controls in endocrine tumors often are not associated with oncogenes common to other tumor types, suggesting that unique pathways govern endocrine proliferation. Within the pancreas, for example, activating mutations of the prototypical oncogene KRAS drive proliferation in all pancreatic ductal adenocarcimomas but are never found in pancreatic endocrine tumors. Therefore, we asked how cellular context impacts K-RAS signaling. We found that K-RAS paradoxically suppressed, rather than promoted, growth in pancreatic endocrine cells. Inhibition of proliferation by K-RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS-activated proproliferative RAF/MAPK pathway by tumor suppressor menin. Consistent with this model, a glucagon-like peptide 1 (GLP1) agonist, which stimulates ERK1/2 phosphorylation, did not affect endocrine cell proliferation by itself, but synergistically enhanced proliferation when combined with a menin inhibitor. In contrast, inhibition of MAPK signaling created a synthetic lethal interaction in the setting of menin loss. These insights suggest potential strategies both for regenerating pancreatic β cells for people with diabetes and for targeting menin-sensitive endocrine tumors.
Strengthening the Informed Consent Process in International Health Research through Community Engagement: The KEMRI-Wellcome Trust Research Programme Experience
Authors: Mwanamvua Boga, Alun Davies, Dorcas Kamuya, Samson M. Kinyanjui, Ester Kivaya, Francis Kombe, Trudie Lang, Vicki Marsh, Bibi Mbete, Albert Mlamba, Sassy Molyneux, Stephen Mulupi, Salim Mwalukore
Journal: PLoS Medicine (2011)

Samson Muchina Kinyanjui and colleagues from the KEMRI-Wellcome Trust Research Programme discuss how they modified their informed consent processes by taking into account local social, cultural, and economic contexts in the design and administration of consent forms.
The Practical Application of the Hydrogen Sensitive Platinum Tipped Electrode in the Diagnosis of Left-to-Right Shunts.
Authors: James C. Hurlburt
Journal: Annals of Internal Medicine (1965)

s1 November 1965The Practical Application of the Hydrogen Sensitive Platinum Tipped Electrode in the Diagnosis of Left-to-Right Shunts.James C. Hurlburt, M.D., Charles E. Rackley, M.D., Charles W. Harris, M.D., Walter L. Floyd, M.D., Edward S. Orgain, M.D., F.A.C.P.James C. Hurlburt, M.D.Search for more papers by this author, Charles E. Rackley, M.D.Search for more papers by this author, Charles W. Harris, M.D.Search for more papers by this author, Walter L. Floyd, M.D.Search for more papers by this author, Edward S. Orgain, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-906_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA new technique, utilizing a hydrogen-sensitive, platinum-tipped wire electrode introduced percutaneously by a no. 18 Cournand needle into the brachial vein and flow directed into the right heart chambers and pulmonary artery, has greatly simplified the detection of left-to-right intracardiac shunts. The electrode position is identified by intracavitary electrocardiographic monitoring. Electrical potential, created by contact of inhaled hydrogen with the platinum tip produces characteristic electrocardiographic deflections when left-to-right shunts are present.Catheterizations in 182 patients have yielded 86 positive, 115 negative and 3 equivocal shunt curves. Fifty-three instances (45 positive and 8 negative) have been confirmed by cardiac catheterization and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Denver, Colorado PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 906-906KeywordsCatheterizationElectrocardiographyHeartPulmonary arteriesVeins Issue Published: 1 November 1965 PDF downloadLoading ...
Funding and Practice of Biomedical Research
Authors: John F. Staropoli
Journal: JAMA (2003)

ONE SIGN THAT THE ALLIANCE BETWEEN ACADEMIA AND LIFE-SCIENCE corporations has become significantly closer since the 1980s is that industry now provides about 70% of all funding for clinical drug trials in the United States. Similarly, many academic nutrition departments are entirely underwritten by corporations, and more than half of the advisors to the US Food and Drug Administration have financial relationships with pharmaceutical companies. These ties may create conflicts of interest that, for instance, compromise the scientific and peer-review processes, prevent the timely dissemination of data, and complicate the monitoring of public health advances. In principle, though, the financial goal of industry—the rapid development of safe, effective drugs—should happily converge with the hopes of clinicians and patients for new treatments. But the financial success of a drug often lies as much in the packaging of its research results as in its potential therapeutic effect. In this issue of MSJAMA, Sameer Chopra surveys the conflicts of interest that can arise when industry is directly involved in acquiring and interpreting data from clinical trials. He underscores the need for transparency and intellectual freedom in biomedical research and also highlights the role of journal editors as guardians of research integrity. Peter Whitehouse discusses how investigators themselves have attempted to rein in financial conflicts during drug development for Alzheimer disease. Rigorous extramural or self-imposed oversight of research activities can go only so far, however, to serve the public health. As long as biomedical research retains its mostly for-profit structure, the invisible hand of the market will likely fail to realign research expenditures according to disease burden. Alexander Iribarne discusses the challenges in developing treatments for “orphan” conditions, which include diseases that are rare or endemic to developing countries. He describes how legislative incentives and public-private partnerships can encourage the development of “orphan” drugs that would otherwise have low market potential. Perhaps just as important as showing a robust therapeutic effect of a new drug over a placebo or first-generation control is a thorough cataloging of negative clinical trial results. One in 1000 drug candidates goes to trial, and of these, 80% are rejected at phase 1 or beyond. Unfortunately, clinicians seldom learn of these negative results. Just as a pertinent negative in a patient’s clinical history can whittle down a differential diagnosis or the publication of a negative genetic association can refocus basic research, so too could negative trial data nudge researchers toward more promising disease targets. Active disclosure of such findings could only enhance the alliances whose financial or altruistic motives ultimately serve the public health.
Oxidized LDL damages endothelial cell monolayer and promotes thrombocyte adhesion
Authors: B. Liu, A. Sidiropoulos, B. Zhao, R. Dierichs
Journal: American Journal of Hematology (1998)

The influence of oxidized low density lipoprotein (LDL) on a human endothelial cell monolayer was examined. The resulting contraction of the oxidized LDL-damaged endothelial cells lets intercellular spaces become enlarged and therefore visible via light microscopy. Electron microscopy reveals that the structural damage facilitates thrombocyte adhesion and formation of microthrombi. Oxidized LDL appears to play a pivotal role in initiating and deteriorating thromboembolic complications. Am. J. Hematol. 57:341–343, 1998. © 1998 Wiley-Liss, Inc.
Letter: Chronic brucellosis.
Authors: D J Payne
Journal: BMJ (1974)

221 exposures 4-5 days, figures which are very sinilar to those in our published series (11-7, 6-7, 4-6, 5-3 and 4-5 days respectively).We excluded fromn our analysis one patient found at necropsy to have a carcinoma of the bile duct and another with abnormal liver function tests who did not actually become jaundiced.More than 25 further cases were reported or followed up too late for inclusion in the analysis.Dr. M. H. M. Dykes and his colleagues (30 March, p. 638) referred to our omission of details of statistical tests and to the "'unquestioned qualifications of the statistical consultants available to the authors."It was precisely because of the latter and because all the data were displayed in our paper that we did not burden readers with details of the sumerous tests that were performed.A Mann-Whitney U test on the pooled doubleand triple-exposure groups com- pared with the single exposure groups gave a value (of U) such that the nornal deviate (z) equalled 2-94 (P=0-0016, single-tailed).Several t-tests on the raw data and on various transformations of the data gave results which were consistent with the non- parametric test.It is not possible to oompare Professor Simpson's 175 post-halothane cases with our own series.Indeed, his letter suggests that the two series are not oomparable in at least one important respect.The mortality of
Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis.
Authors: M Bourdi, D Larrey, J Nataf, J Bernuau, D Pessayre, M Iwasaki, F P Guengerich, P H Beaune
Journal: Journal of Clinical Investigation (1990)

Sera from patients with dihydralazine-induced hepatitis were shown to contain anti-liver microsomal autoantibodies (anti-LM) by indirect immunofluorescence. These anti-LM antibodies were different from anti-liver/kidney microsomes (anti-LKM) 1 or 2 autoantibodies which have been previously described. Sera recognized a single 53,000 = Mr polypeptide in human liver microsomes as judged by immunoblotting, and the target antigen was identified as cytochrome P-450IA2 (P-450IA2) by (a) comparison of immunoblotting patterns with anti-human P-450IA2 and anti-rat P-450IA2 and with five anti-LM sera, and (b) specific immunoinhibition of microsomal ethoxyresorufin and phenacetin O-deethylation activities (both P-450IA2 supported reactions) by anti-LM antibodies. Finally, purified human P-450IA2 was recognized by these anti-LM sera. The anti-LM antibodies are specific for the disease because none of the other antisera tested behaved in the same manner as anti-LM, even those from patients treated with dihydralazine and without hepatic disease. A possible role of P-450IA2 in the metabolism of dihydralazine was suggested by competitive inhibition of ethoxyresorufin-O-deethylase observed in microsomal incubations. Thus, a new example is presented in which a cytochrome P-450 may be a target for autoantibodies in drug-induced hepatitis.
Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts.
Authors: K P Burton, J G Jones, T H Le, A D Sherry, C R Malloy
Journal: Circulation Research (1994)

The effects of a xanthine oxidase-mediated free radical-generating system containing purine and iron-loaded transferrin or solutions containing hydrogen peroxide and iron-loaded transferrin on substrate utilization and high-energy phosphates were evaluated by nuclear magnetic resonance (NMR) spectroscopy in isolated perfused rat hearts. Hearts were supplied with lactate, acetate, and glucose, and the contribution of each substrate to acetyl coenzyme A was measured in control hearts and in the presence of a free radical-generating system. Perfused hearts were monitored by 31P NMR, and tissue extracts were analyzed by 13C NMR. Free radicals decreased the phosphocreatine and beta-ATP peak areas and reduced contractile function. Under control conditions, lactate, acetate, and endogenous sources were the major contributors of acetyl coenzyme A units, with only 5% originating from glucose. In the presence of a xanthine oxidase-mediated free radical-generating system, the glucose contribution increased to 54%, while contributions from acetate and endogenous sources were significantly reduced. Both 13C and 31P NMR analyses showed no significant accumulation of glycolytic sugar phosphates, suggesting little inhibition of glyceraldehyde-3-phosphate dehydrogenase. The increased contribution of glucose to the tricarboxylic acid cycle relative to acetate and endogenous sources is consistent with activation of pyruvate dehydrogenase. In contrast, hearts exposed to a hydrogen peroxide-based free radical-generating system showed an increase in lactate utilization, a decrease in acetate utilization, and no change in glucose utilization compared with control hearts. Glycolytic sugar phosphates were found to accumulate, suggesting possible inhibition of glyceraldehyde-3-phosphate. Thus, different radicals or their metabolites may have varying effects on myocardial metabolism.
P1226 NS3 Q80K DID NOT IMPACT EFFICACY OR TREATMENT-EMERGENT RESISTANCE PATTERNS IN HCV GENOTYPE 1-INFECTED PATIENTS RECEIVING FALDAPREVIR + PEGINTERFERON/RIBAVIRIN IN THREE PHASE III TRIALS
Authors: K. Berger, C. Sarrazin, P. Ferenci, D.M. Jensen, I.M. Jacobson, J.O. Stern, A.-M. Quinson, J. Scherer, G. Kukolj
Journal: Journal of Hepatology (2014)
Pharmacokinetic aspects and in vitro–in vivo correlation potential for lipid-based formulations
Authors: Sivacharan Kollipara, Rajesh Kumar Gandhi
Journal: Acta Pharmaceutica Sinica B (2014)

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal tract. These formulations offer multiple advantages such as reduction in food effect and inter-individual variability, ease of preparation, and the possibility of manufacturing using common excipients available in the market. Despite these advantages, very few products are available in the present market, perhaps due to limited knowledge in the in vitro tests (for prediction of in vivo fate) and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral administration. The current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations, their pharmacokinetic aspects and in vitro in vivo correlation (IVIVC) perspectives. Various pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion, bioavailability enhancement mechanisms, impact of excipients on efflux transporters, and lymphatic transport are discussed with examples. In addition, various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation, in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.
Recent Advances in Stress Signaling in Cancer
Authors: Chantale I. Morin, Jacques Huot
Journal: Cancer Research (2004)

Abstract This meeting brought together some of the world’s leading scientists in the field of stress signaling, apoptosis, and cancer. This resulted in a productive interaction that updated our current knowledge on “Stress Signaling in Cancer.” It comes out that subtle disturbances in cell signaling can be associated with and even lead to cancer. As a corollary, it appears that correcting the signaling defects associated with cancer constitutes a new approach to the treatment and control of neoplastic diseases. The meeting also raised several questions that should be addressed. In particular, it is of the utmost importance to better understand the mechanisms that underlie the specificity of the cellular response with regard to different ligands. For example, why does Gadd45b prevent apoptotic cell death in response to tumor necrosis factor α, whereas it favors apoptosis after transforming growth factor β (E. De Smaele et al., Nature (Lond.), 414: 308–313, 2001; J. Yoo et al., J. Biol. Chem., 278: 43001–43007, 2003). Other questions concern the understanding of the cross-talk mechanisms between different stress and apoptotic pathways and how the strength and the position and timing of a signal may affect different pathways. The next few years of research in this field should be enlightening and fruitful.
TECK: A Novel CC Chemokine Specifically Expressed by Thymic Dendritic Cells and Potentially Involved in T Cell Development
Authors: Alain P Vicari, David J Figueroa, Joseph A Hedrick, Jessica S Foster, Komal P Singh, Satish Menon, N.G Copeland, D.J Gilbert, N.A Jenkins, Kevin B Bacon, Albert Zlotnik
Journal: Immunity (1997)
Risk to Offspring of Parents With Congenital Heart Defects
Authors: James J. Nora
Journal: JAMA (1969)

The occurrence risk of atrial-septal defect (ASD) and ventricular-septal defect (VSD) was determined in children of 308 adults with these heart lesions, most of which had been surgically corrected. Parents with ASD had 2.6% of their children affected with ASD which is 37 times greater than the estimated population frequency. For VSD, 3.7% of the children of parents with this heart defect were similarly affected. This is 21 times the estimated population frequency. These findings are offered as empirical risk figures for the purposes of genetic counseling. The data were found to approximate closely the predictions of multifactorial inheritance hypothesis for the etiology of congenital heart diseases. In comparing the congenital heart patients with the general population, differences in marriage patterns were detected which could influence fertility and partially offset the increased recurrence risk.
A case of asthma.
Authors: H W Fladee
Journal: BMJ (1976)

surely this is sledge-hammer treatment: not all cases go on to develop true rheumatoid arthritis with permanent joint changes and in any case if this happens the disease may well turn out to be mild and easily controlled by simpler measures.The potential hazards of penicillamine, especially the immune complex nephropathy, should not be taken too lightly.Dr Huskisson states "it is a consider- able advantage that D-penicillamine can be used in a small dose [250 mg daily] which is unlikely to cause side effects," but many rheumatologists feel that penicillamine.nephropathy, which may persist for years, is not dose-related.While classic palindromic rheumatism is characterised by bouts of very severe joint
Expression profiling of the estrogen responsive genes for evaluation of estrogen activity among natural estrogens and industrial chemicals using a customized DNA microarray
Authors: Shunichi Terasaka, Aita Aita, Akio Inoue, Shinichi Hayashi, Michiko Nishigaki, Kazuhiko Aoyagi, Hiroki Sasaki, Yuko Wada-Kiyama, Yasuo Sakuma, Shuichi Akaba, Junko Tanaka, Hideko Sone, Junzo Yonemoto, Masao Tanji, Ryoiti Kiyama
Journal: Environmental Health Perspectives (2004)
Malignant Solid Tumors in Children: A Review
Authors: Beatrice C. Lampkin
Journal: JAMA (1981)

This book, in ten chapters and an epilogue, provides an overview of cancer in children and an up-to-date perspective on the diagnosis and treatment of five common childhood malignancies. In the first chapter, the author analyzes the data on incidence, childhood deaths, and tumor types given in the Third National Cancer Survey, the Surveillance Epidemiology and End Results Program of the National Cancer Institute, and other published series. Etiology, genetic considerations, strategy and tactics of cancer therapy, concepts of prognosis, and clinical research are also discussed. In the second chapter he reviews the systematic approach to treatment of a child who may have a solid malignant neoplasm. Principles of therapy are discussed in chapter 3. These chapters are particularly good for medical students, house staff, and practicing physicians. Particularly useful to pediatric hematologists, oncologists, and fellows in training is the next chapter on the response of various solid malignant neoplasms