tbuckley/cabot-search huggingface dataset:
Abstract 3061: Colocalization of NQO1 with the mitotic spindle in human cells
Authors: David Siegel, Jadwiga K. Kepa, David Ross
Journal: Cancer Research (2012)

Abstract NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes the two-electron reduction of quinones. NQO1 has also been shown to reduce superoxide to hydrogen peroxide and regulate ubiquitin independent 20S proteasome degradation of proteins such as p53. In normal tissues NQO1 is expressed primarily in epithelium, endothelium and adipocytes where it is believed to play a protective role. NQO1 is also expressed at relatively high levels in many human solid tumors where it has been targeted for its ability to bioactivate anti-tumor quinones. Interestingly, immunohistochemical staining for NQO1 expression in formalin-fixed human non-small cell lung cancer tissue sections revealed strong staining for NQO1 on the mitotic spindles of cells in mitosis. Immunocytochemical studies in combination with confocal microscopy using human nontransformed and transformed cells (HUVEC, HBMEC, astrocytes) as well as human cancer cell lines confirmed NQO1 staining of mitotic spindles. Staining of mitotic spindles for NQO1 was not observed in cells genotyped as homozygous for the NQO1*2 polymorphism or in cells pretreated with siRNA directed against NQO1. Double-labeling experiments using anti-alpha-tubulin and anti-NQO1 antibodies demonstrated colocalization of NQO1 with spindle microtubules. Pretreatment with NQO1 inhibitors (ES936 or dicumarol) did not prevent binding of NQO1 to mitotic spindles suggesting that binding is independent of the redox state of the enzyme. In cells not undergoing mitosis there was no apparent association of NQO1 with the cytoskeleton suggesting that binding of NQO1 to microtubules may be specific for mitotic spindles. Previous immunocytochemical studies by other investigators have shown that p53 and 20S proteasome could also be found in association with the mitotic spindle. Whether NQO1 binds directly to spindle microtubules or the binding of NQO1 to the spindle is dependent upon the association with other proteins such as p53 or 20S proteasome is currently under investigation (Supported by NIH grant R01ES018943). 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 3061. doi:1538-7445.AM2012-3061
Delineation of a defect in T cell receptor beta genes of NZW mice predisposed to autoimmunity.
Authors: D J Noonan, R Kofler, P A Singer, G Cardenas, F J Dixon, A N Theofilopoulos
Journal: The Journal of Experimental Medicine (1986)

In an attempt to determine whether genes involved in T cell antigen recognition are structurally abnormal and thereby promote murine systemic lupus, we analyzed the structural integrity of the D, J, and C region elements of the T cell receptor alpha and beta chain genes in all major lupus strains and several normal strains. Within the limits of restriction fragment length polymorphism analysis, all strains had an identical genomic organization, except the NZW mice, in which a deletion of the C beta 1-D beta 2-J beta 2 elements was found. Sequence analysis of NZW genomic elements containing this deletion placed its probable origin within the first exon of C beta 1, and extending to a complementary region within the first exon of C beta 2. The significance of this abnormality in the pathogenesis of systemic autoimmune disease remains to be determined.
Body surface mapping during endocardial pacing at multiple left and right ventricular sites: QRS variability in patients without structural heart disease
Authors: Arne SippensGroenewegen, Hans Spekhorst, Norbert M. van Hemel, J.Herre Kingma, Richard N.W. Hauer, Michiel J. Janse, Arend J. Dunning
Journal: Journal of the American College of Cardiology (1990)
Hepatic regulation of platelet-activating factor acetylhydrolase and lecithin: Cholesterol acyltransferase biliary and plasma output in rats exposed to bacterial lipopolysaccharide
Authors: Stanislav I. Svetlov, Ekkehard Sturm, Merle S. Olson, James M. Crawford
Journal: Hepatology (1999)

Normal rat bile contains secretory platelet-activating factor acetylhydrolase (PAF-AH), the enzyme capable of hydrolyzing the inflammatory mediator platelet-activating factor (PAF), and phospholipids containing oxidized truncated fatty acids. Because lecithin:cholesterol acyltransferase (LCAT) possesses intrinsic PAF-AH-like activity, it also may represent a potential anti-inflammatory enzyme. The behavior of PAF-AH and LCAT in hepatobiliary inflammatory responses in vivo has not been characterized. We therefore investigated the biliary and plasma secretion and pharmacological characteristics of these enzymes in rats subjected to intraportal bacterial endotoxin exposure (lipopolysaccharide [LPS], Escherichia coli , 055:B5). Portal vein LPS infusion (1 mg/kg, bolus) resulted in a maximal 4- to 5-fold increase in bile PAF-AH-specific activity with a gradual decline to baseline by 18 hours. Biliary PAF-AH hydrolyzed also the truncated sn-2-succinoyl and sn-2-glutaroyl analogs of PAF, indicating a broader activity of PAF-AH in bile toward byproducts of glycerophospholipid peroxidation. Plasma PAF-AH activity was not altered 5 hours after LPS injection compared with saline injection, but it was significantly elevated 18 hours after endotoxin exposure. The levels of LCAT in bile were low and declined to nearly undetectable values by 5 hours after cannulation in both control and LPS-exposed rats. Plasma LCAT activity was significantly increased after 5 hours and decreased 18 hours after LPS injection. In summary, hepatic exposure to endotoxin results in a rapid increase in biliary secretion of PAF-AH followed by elevation of LCAT and PAF-AH levels in plasma. We propose that biliary secretion of PAF-AH may be involved in the hepatic response to endotoxic insult by counteracting potential inflammatory damage in the biliary tree and gastrointestinal tract, whereas plasma increases in LCAT and PAF-AH may promote elimination of excess PAF and oxidized phospholipids in the circulation
ON THE COVERON THE COVER
Authors: Rahul Rajkumar
Journal: JAMA (2003)

A FRIEND drew my attention to a chapter in Robert Zussman's book, Intensive Care.In this chapter, an intern on an ICU rotation reports a bizarre dream in which he finds penguins in a basement.In order to save one of these penguins, who can only survive in a cold environment, he puts it in a blender with some ice and turns the blender on. 1 For me, the enduring lesson of my time in the ICU was that bad things can sometimes happen to people in the hospital.Sometimes a treatment can be worse than the disease itself.Sometimes our efforts seem only to prolong a patient's suffering.Many medical students have had a similar ICU experience at some point in their training; from this, it requires no great leap of reasoning to reconsider the role of the physician in addressing pain and suffering.Should unwilling patients be allowed to forgo life-sustaining therapy?Most systems of law concede this right.But this raises a more difficult question: Should physicians assist certain patients-perhaps those who meet some predefined criteria for measuring distress-in ending their own lives?Within the medical profession and among ethicists there are strong opinions, but there is no widely agreed-upon answer.Perhaps mirroring or perhaps causing this conflicted thinking, lawmakers in our country are similarly divided.In 1997, the US Supreme Court ruled that the Constitution neither explicitly permits nor prohibits physician-assisted suicide.Since then, the states have been free to consider on their own the question of legalizing the practice of assisted suicide.Measures to legalize physician-assisted suicide have been proposed and defeated in eight state legislatures-bringing the number of states outlawing its practice to 38.Oregon, which held a popular referendum on this issue in 1994, became the only state to legalize assisted suicide by implementing its Death With Dignity Act in 1997. 2 In this issue of MSJAMA Juan Carlos Batlle clarifies terminology in recounting the legal and historical differences among assisted suicide, euthanasia, and the withdrawal of life support.Joanne Lynn and Karl Lorenz examine some of the ethical problems that physicians might face in responding to a patient's request for assisted suicide and draw attention to the failure of the US health care system to provide reliable supportive and palliative care for the dying.Larry Palmer sizes up the legal struggle between the US attorney general and the state of Oregon over that state's assisted suicide law.All of these authors challenge us to think about this issue, which yields no easy answers.
Assessing risk associated with carotid endarterectomy. A statement for health professionals by an Ad Hoc Committee on Carotid Surgery Standards of the Stroke Council, American Heart Association.
Authors: H G Beebe, G P Clagett, J A DeWeese, W S Moore, J T Robertson, B Sandok, P A Wolf
Journal: Circulation (1989)

This position statement provides guidelines for assessing risk associated with carotid endarterectomy and defines the point at which risk is too high to perform surgery for specific indications described below. Morbidity and mortality levels are discussed. This statement does not address indications for surgery or merits of specific medical or surgical treatments. Results of current studies that compare relative risk of various treatments for carotid artery disease are not yet available.
Phase II Study of a 3-Day Schedule with Topotecan and Cisplatin in Patients with Previously Untreated Small Cell Lung Cancer and Extensive Disease
Authors: Morten Sorensen, Ulrik Lassen, Peter Buhl Jensen, Kell Østerlind, Nina Jeppesen, Britta Bjerregaard Jensen, Anders Mellemgaard, Carsten Rytter, Seppo Wang Langer
Journal: Journal of Thoracic Oncology (2008)
Terminology and classification of acute mountain sickness.
Authors: J G Dickinson
Journal: BMJ (1982)

There are several unsolved questions about acute mountain sickness.Climbers and trekkers want to know how to recognise cases, how to assess their severity, and how to act to avoid deaths.They also need clear guidance about prevention, a subject that has stimulated much correspondence after recent articles.1 2 Medical scientists who are called on to advise on these matters have many fascinating puzzles about the nature of acclimatisation and the disordered physiology that leads to the various manifes- tations of acute mountain sickness.Solution of these problems could be helped only by agreement on a logical terminology and classification of acute mountain sickness.In my opinion many of the terms currently used (table ) seem to prejudge unsolved pathophysiological questions, render the training of unqualified personnel difficult, and are, Terms used to describe acute mountain sickness
The cytological features of<i>NPM1</i>-mutated acute myeloid leukemia
Authors: Barbara J. Bain, Marc Heller, Sarmad Toma, Jiří Pavlů
Journal: American Journal of Hematology (2015)

A 69-year-old woman with a previous history of type 2 diabetes mellitus presented with a 2-week history of worsening abdominal pain, reduced oral intake, and lethargy. She was pyrexial (39°C) with a sinus tachycardia. Her full blood count showed: hemoglobin concentration 119 g/l, white cell count 151.5 × 109/l, and platelet count 33 × 109/l. The blood film showed many circulating blast cells. These were of medium size with a high nucleocytoplasmic ratio. Many of them had an indentation in the nucleus, producing a cup-like shape when viewed in profile; when viewed from above, the invagination sometimes simulated a giant nucleolus (images). Nuclear indentations were apparent also in smear cells. Cytoplasmic basophilia varied from moderate to strong. A minority of basophilic blast cells had cytoplasmic blebs. Some blast cells contained Auer rods, usually one but up to three per cell, these often being related to the nuclear indentation. The cytological features were considered strongly suggestive of acute myeloid leukemia (AML) with NPM1 mutation and further investigations were arranged. A bone marrow aspirate showed 89% blast cells with similar cytological features to those in the peripheral blood. Flow cytometry gated on the blast population showed expression of CD33, CD117 and CD123 with partial expression of HLA-DR and myeloperoxidase. CD34 was not expressed. Blast cells were also negative for CD13, CD11b, CD14, CD64, CD56, and CD7. Standard cytogenetic analysis yielded no metaphases but molecular analysis showed both a 4 bp insertion in NPM1 and a FLT3-internal tandem duplication (ITD) of 24 bp. The patient responded to broad-spectrum antibiotics without a focus of infection being identified, and entered complete remission following the initial course of cytarabine and daunorubicin. Cup-shaped blast cells are associated with NPM1 mutation, particularly when there is coexisting FLT3-ITD.1, 2 They can also occur with AML associated with FLT3-ITD without NPM1 mutation. The nuclear pockets are shown on ultrastructural examination to be occupied by a collection of mitochondria, lysosomes and endoplasmic reticulum.1, 2 The light microscopy features of NPM1-mutated AML are sufficiently distinctive to suggest this diagnosis. The CD34-negativity, often with HLA-DR also being negative, could lead to confusion with the variant form of acute promyelocytic leukemia but the nuclear shape differs.
Anticholinergic Therapy: A Triple Threat to Lower Esophageal Sphincter Competence.
Authors: Sidney Cohen
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Anticholinergic Therapy: A Triple Threat to Lower Esophageal Sphincter Competence.Sidney Cohen, M.D., William Lipshutz, M.D.Sidney Cohen, M.D.Search for more papers by this author, William Lipshutz, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-792_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMedical treatment for symptomatic gastroesophageal reflux and peptic esophagitis consists of reducing gastric acidity and reducing gastroesophageal reflux. Anticholinergic medications are effective in diminishing acid secretion, but their effect on lower esophageal sphincter competence, the prime barrier to prevention of reflux, is conflicting. The present study was designed to determine whether anticholinergic medications affect [1] resting lower esophageal sphincter competence, [2] intrinsic adaptive changes in the sphincter competence to changes in intra-abdominal pressure, and [3] adaptive changes in sphincter competence to endogenous gastrin release. Lower esophageal sphincter pressure measurements using an infused open-tipped recording system were made in 20 normal... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDifferential effect of atropine on rightward and leftward lower esophageal sphincter pressureNeurohumoral, hormonal, and drug receptors for the lower esophageal sphincterPhysiologyA Comparison of the Site of Action of Gastrin I on Lower Esophageal Sphincter and Antral Circular Smooth Muscle 1 May 1970Volume 72, Issue 5Page: 792-792KeywordsGastrinGastroesophageal reflux disease Issue Published: 1 May 1970 PDF DownloadLoading ...
Liver Disease and Hyperthyroidism
Authors: JON D. GREEN
Journal: Annals of Internal Medicine (1979)

Letters and Corrections1 July 1979Liver Disease and HyperthyroidismJON D. GREEN, M.D., DAVID STRASSBERG, M.D.JON D. GREEN, M.D.Search for more papers by this author, DAVID STRASSBERG, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-1-129_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We have read with interest the article by Cooper and co-authors in the February issue (1). In their discussion, the authors suggest that hyperthyroid patients with an elevated alkaline phosphatase and a normal 5′nucleotidase may be spared needless diagnostic evaluation when they present with these blood chemistry values. We have recently seen a patient with thyrotoxicosis; evaluation of her alkaline phosphatase elevation revealed hepatobiliary disease.A 68-year old woman was admitted to hospital because of palpitations. Heat intolerance and an 11.3-kg weight loss had occurred over the past year. She denied abdominal pain or nausea but avoided...Reference1. COOPERKAPLANRIDGWAYMALOOFDANIELS DMEFG. Alkaline phosphatase isoenzyme patterns in hyperthyroidism. Ann Intern Med. 1979;90:164-8. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: JON D. GREEN, M.D.; DAVID STRASSBERG, M.D.Affiliations: 204 Walnut Street; Livingston, NJ 07039 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byYinning Tablet, a hospitalized preparation of Chinese herbal formula for hyperthyroidism, ameliorates thyroid hormone-induced liver injury in rats: Regulation of mitochondria-mediated apoptotic signals 1 July 1979Volume 91, Issue 1Page: 129-129KeywordsAbdominal painBlood chemistryHyperthyroidismLiver diseasesNauseaPhosphatasesWeight loss ePublished: 1 December 2008 Issue Published: 1 July 1979 PDF downloadLoading ...
610 STRONG IN VIVO ANTIVIRAL EFFICACY OF A NEW L-DEOXYCYTIDINE DERIVATE IN HEPATITIS B VIRUS INFECTED HUMAN HEPATOCYTES REPOPULATING THE LIVER OF UPA/SCID MICE
Authors: E. Matthes, T. Volz, M. Lütgehetmann, J. Petersen, M. Dandri
Journal: Journal of Hepatology (2010)
Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis†
Authors: Stephen H. Caldwell, Luiz Antonio R. de Freitas, Sang H. Park, Maria Lucia V. Moreno, Jan A. Redick, Christine A. Davis, Barbee J. Sisson, James T. Patrie, Helma Cotrim, Curtis K. Argo, Abdullah Al‐Osaimi
Journal: Hepatology (2009)

Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well-documented morphological abnormality seen on transmission electron microscopy in this disease. It has been suggested that IMCs consist of phospholipids, but their exact composition remain uncertain many years after their discovery. Micellar phase transitions of phospholipid bilayers is a well-known but little-studied phenomenon in living systems. Its presence in the mitochondria of NASH would offer significant insight into the disease with possible therapeutic implications. We postulated that intramitochondrial disturbances in NASH are sufficient to produce such transitions and that their detection in fresh biopsies would therefore be a dynamic process. To test this, we performed a blinded, prospective analysis of fresh liver biopsy samples immediately fixed under different conditions. Quantitative transmission electron microscopy morphometry, performed by systematically counting total mitochondria and IMCs within areas of uniform dimension, showed a stepwise decline in IMCs with cooler fixation temperature in each subject studied. Randomization testing (Monte Carlo resampling) confirmed that the detection of IMCs was strongly dependent on fixation temperature (P < 0.0001). Conclusion: These results indicate that the intramitochondrial crystals characteristic of NASH are highly dynamic and unstable structures. The findings offer the strongest support yet for their origin in micellar phase transitions. We speculate that such transitions result from microenvironmental changes within the mitochondria and carry therapeutic implications, especially in regard to dietary manipulations of mitochondrial lipid composition. (HEPATOLOGY 2009.)
Specificity of anti-Sm antibodies by ELISA for systemic lupus erythematosus: increased sensitivity of detection using purified peptide antigens.
Authors: M Field, D G Williams, P Charles, R N Maini
Journal: Annals of the Rheumatic Diseases (1988)

Sm antigen was purified by immunoaffinity chromatography using a murine monoclonal anti-Sm antibody and was confirmed to be free from contaminating polypeptides. This was then used to detect anti-Sm antibodies in patients' sera by enzyme linked immunosorbent assay (ELISA). Antibodies against Sm were detected in only 9/52 (17%) patients with systemic lupus erythematosus (SLE) by immunodiffusion, but 15/52 (29%) were positive for IgG anti-Sm antibodies by ELISA. The presence of anti-Sm antibodies remained disease specific despite the increase in sensitivity of this assay and validates its potential use for clinical application. There was no correlation between the presence of anti-Sm antibodies and any clinical features of SLE. In 23 renal biopsies a membranous component to the glomerulonephritis correlated with anti-Sm antibodies (p less than 0.05). Patients from West Africa, the Carribean Islands, and Asia had a higher prevalence of anti-Sm antibodies than the local Caucasian population.
DISSECTING ABSCESS OF THE ABDOMINAL WALL PRODUCING DEFORMITY SIMULATING POTT'S DISEASE.
Authors: JAMES B. BULLITT
Journal: JAMA (1901)

The case which forms the basis of this report presents features which render it of sufficient interest, it is believed, to warrant its presentation to this Section. The patient was a lad of 16, who was taken sick in January, 1900, with a typical attack of typhoid fever. He remained In bed six weeks, when, on getting up after the subsidence of the fever, there was observed a certain amount of inability to raise the left leg in drawing on the trousers. By the middle of May he developed a general antero-posterior curvature of the spine from the sacrum up with a lateral deviation with the convexity to the right side, and at this time was seen by Dr. Ap M. Vance of Louisville. There was some fever at the time, though no record was kept, and there was a certain fulness in the right loin which caused a suspicion