tbuckley/cabot-search huggingface dataset:
Tobacco Smoke Exposure in Either the Donor or Recipient Before Transplantation Accelerates Cardiac Allograft Rejection, Vascular Inflammation, and Graft Loss
Authors: Ashwani K. Khanna, Jianping Xu, Patricia A. Uber, Allen P. Burke, Claudia Baquet, Mandeep R. Mehra
Journal: Circulation (2009)

Tobacco exposure in cardiac transplant recipients, before and after transplantation, may increase the risk of cardiac allograft vasculopathy and allograft loss, but no direct evidence for this phenomenon is forthcoming. In this experimental study, we investigated early consequences of tobacco smoke exposure in cardiac transplant donors and recipients with an emphasis on alloinflammatory mediators of graft outcome.Using heterotopic rat cardiac transplantation, we tested the effects of donor or recipient tobacco smoke exposure in 6 groups of animals (rat heterotopic cardiac transplantation) as follows: tobacco-naïve allogeneic rejecting controls (n=6), tobacco-naïve nonrejecting controls (n=3; killed on day 5 to simulate survival times of tobacco-treated animals), isografts (n=3), both donor and recipient rats exposed to tobacco smoke (n=4), only donor rats exposed to tobacco smoke (n=7), and only recipient rats exposed to tobacco smoke (n=6). Polymerase chain reaction studies of tissue and peripheral (systemic) protein expression were performed to evaluate inflammatory (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune (interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) pathways, as was histological analysis of the cardiac allografts. Our experiments reveal that pretransplantation tobacco exposure in donors and/or recipients results in heightened systemic inflammation and increased oxidative stress, reduces posttransplantation cardiac allograft survival by 33% to 57%, and increases intragraft inflammation (tumor necrosis factor-alpha, interferon-gamma, interleukin-6) and alloimmune activation (CD3, interleukin-1 receptor 2, programmed cell death-1, and stromal cell-derived factor-1) with consequent myocardial and vascular destruction.These sentinel findings confirm that tobacco smoke exposure in either donors or recipients leads to accelerated allograft rejection, vascular inflammation, and graft loss. Molecular pathways that intersect as arbiters in this phenomenon include instigation of alloimmune activation associated with tobacco smoke-induced inflammation.
Dabigatran was noninferior to warfarin for preventing recurrent venous thromboembolism
Authors: Esteban Gandara
Journal: Annals of Internal Medicine (2010)

ACP Journal Club20 April 2010Dabigatran was noninferior to warfarin for preventing recurrent venous thromboembolismEsteban Gandara, MDEsteban Gandara, MDUniversity of Ottawa, Ottawa, Ontario, Canada (E.G.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-8-201004200-02007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSchulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342-52. https://pubmed.ncbi.nlm.nih.gov/19966341Clinical Impact RatingsEmergency Med: Hospitalists: Hematology: References1 Connolly SJ, Pogue J, Eikelboom J, et al, for the ACTIVE W Investigators. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008;118:2029-37. [PMID: 18955670] Google Scholar2 van Walraven C, Oake N, Wells PS, Forster AJ. Burden of potentially avoidable anticoagulant-associated hemorrhagic and thromboembolic events in the elderly. Chest. 2007;131:1508-15. [PMID: 17317732] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Ottawa, Ottawa, Ontario, Canada (E.G.)This article was published at Annals.org on 6 April 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNuevos anticoagulantes orales en el tratamiento de la trombosis venosa profunda 20 April 2010Volume 152, Issue 8Page: JC4-7KeywordsAdverse eventsAntiplatelet therapyHemorrhagePatientsPulmonary embolismSafetyThrombinVenous thromboembolism ePublished: 20 April 2010 Issue Published: 20 April 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Genetic control of a shared idiotype among antibodies directed to distinct specificities.
Authors: S T Ju, B Benacerraf, M E Dorf
Journal: The Journal of Experimental Medicine (1980)

We developed an idiotypic radioimmunoassay system that detects shared idiotypic determinants, termed GTGL idiotype, on antibodies bearing distinct antigen-binding specificities in various mouse strains. Either poly-(Glu, Tyr) (GT)- or poly-(Glu, Lys) (GL)-related determinants are able to induce anti-GT and anti-GL (GTGL)-idiotypic antibodies. Strain distribution studies indicate that GTGL-idiotypic antibodies are readily induced and frequently expressed in antisera obtained from 25 different mouse strains immunized either with GT-related or GL-related polymers. The ability to express GTGL-idiotypic antibodies is a dominant trait and is controlled by Igh-linked gene(s). In addition, we demonstrated that in anticopolymer of L-glutamine acid60- L-alanine30-L-tyrosine (GAT) and anticopolymer of L-glutamic acid54-L-lysine35-L-phenylalanine11(GLphi) antisera, both antibodies uniquely specific to GAT or GLphi, respectively, and antibodies bearing dual specificities for GAT and GLphi, expressed GTGL idiotype. The genetic implications of these findings are discussed. X
CATARACT IN CONNECTION WITH CORTICOSTEROIDS
Authors: E. Ask-Upmark
Journal: JAMA (1960)

<h3>To the Editor:—</h3> InThe Journal, Sept. 10, page 166, Black and co-workers reported the occurrence of subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. In their interesting study the authors found a cataract, which ensued after at least one year's treatment with moderate or large doses of steroids. In a previous paper (<i>Acta Med Scand</i><b>149</b>:161, 1954) I called attention to the fact that cataract, as observed in connection with the syndrome of Takayashu ("pulseless disease," "aortic arch syndrome") may be accelerated to a considerable degree even after a short period of treatment with corticosteroids. In this syndrome the nutrition of the cranial structures is poor, and it is possible that this factor may be responsible for the ease with which the cataract may appear.
FDA Regulation of Tobacco — Pitfalls and Possibilities
Authors: Allan M. Brandt
Journal: New England Journal of Medicine (2008)

It is likely that during the coming year, Congress will pass legislation bringing tobacco products under the regulatory authority of the FDA. Allan Brandt writes that it behooves public health advocates and Congress to fully understand all the implications of FDA regulation. View an audio slide presentation in which Dr. Brandt discusses cigarette advertisements in the 20th century. Dr. Allan Brandt discusses the provisions, benefits, and criticisms of legislation that would grant the FDA regulatory authority over tobacco products. Dr. Brandt is a professor of the history of medicine at Harvard Medical School, Boston, and dean of the graduate school of arts and sciences at Harvard University, Cambridge, MA.
Cyclic adenosine monophosphate-stimulated anion transport in rabbit cortical collecting duct. Kinetics, stoichiometry, and conductive pathways.
Authors: V L Schuster
Journal: Journal of Clinical Investigation (1986)

Cyclic AMP stimulates HCO3 secretion and Cl self-exchange in rabbit cortical collecting tubule. We found that varying peritubular [Cl] changed the Cl self-exchange rate with saturation kinetics (Km, 3-4 mM). HCO3 secretion also showed saturation kinetics as a function of mean luminal [Cl] (Km, 4-11 mM). Both Cl self-exchange and Cl-HCO3 exchange thus appear to be carrier-mediated. Addition/removal of basolateral HCO3 qualitatively changed Cl and HCO3 transport as expected for Cl-HCO3 exchange, but quantitatively changed Cl absorption more than HCO3 secretion. The diffusive Cl permeability and the transepithelial conductance in the presence of HCO3/CO2 and cAMP were higher than in their absence suggesting that HCO3/CO2 and cAMP together increase a conductive Cl pathway parallel to a 1:1 Cl-HCO3 exchanger. Thus, cAMP not only stimulates the overall process of anion exchange (probably by increasing an electroneutral exchanger and/or a series Cl conductance), but also stimulates a Cl conductance parallel to the exchange process.
Effects of steriod hormones on human fibroblasts in vitro. II. Antagonism by androgens of cortisol-induced inhibition.
Authors: W Harvey, R Grahame, G S Panayi
Journal: Annals of the Rheumatic Diseases (1976)

Inhibition of dermal activity by cortisol in culture was partially reversed by two naturally occurring androgens, testosterone and dihydrotestosterone. ACTH and the androgen precursor dehydroepiandrosterone sulphate showed not such antagonistic effect. These results suggest that increased production of adrenal androgens during ACTH therapy may account for the relative absnece of 'skin-thinning' and 'steroid-bruising' which are common side-effects of corticosteroid therapy.
Abstract A25: PPP2R1A mutations affect PP2A complex formation, and novel protein interactions in gynecological carcinoma cell lines
Authors: Melissa K. McConechy, Vincent Chen, Gregg Morin, James Brenton, David G. Huntsman
Journal: Clinical Cancer Research (2013)

Abstract Gynecological malignancies (ovarian clear cell and endometrioid carcinomas, endometrial serous, endometrioid and clear cell carcinomas) harbor somatic mutations in the gene PPP2R1A, the scaffolding subunit of the serine/threonine protein phosphatase 2A (PP2A) complex. The PP2A complex is composed of an A (scaffold), C (catalytic) subunit, and different B (regulatory) subunits. The PPP2R1A mutations are proposed to play a role in PP2A B-subunit binding, and thus formation of a functional PP2A phosphatase complex. The aim of this study is to determine how PPP2R1A mutations affect the binding of B-subunits and other novel interactions within the context of ovarian and endometrial carcinomas. The ovarian clear cell line RMG2 and endometrial carcinoma cell lines Hec-1-A and Hec50 all harbor PPP2R1A mutations. The mismatch repair deficient cell line Hec-1-A express a PPP2R1A W257L heterozygous mutation; therefore somatic cell knockout technology was used to generate isogenic PPP2R1A clones that express only mutant PPP2R1A, and clones that express more wild-type than mutant. These Hec-1-A isogenic cell lines were used for PPP2R1A co-immunoprecipiation (Co-IP) followed by MS/MS-SWATHTM analysis to identify PP2A B-subunits and other novel protein interactions. Our preliminary results using Hec-1-A isogenic cell lines suggest that some PP2A B-subunits (PPP2R5D and PPP2R2A) are found to be decreased in abundance in the mutant cell lines. We were able to identify the catalytic subunit (PPP2CA) in PPP2R1A Co-IPs in all cell lines. We also show that PPP2R1A interacts with novel proteins such as histones (Histone 1, Histone H2B type 1-N), ubiquitin ligases (TRIM21) and proteins involved in mitotic control (ANKLE2). Of particular interest we have identified the cancer gene nucleophosmin (NPM1) as a potential novel interactor of PP2A. We have established the isogenic Hec-1-A cell lines as a model system to determine the functional effects of a somatic PPP2R1A mutation. These cell lines have shown that the PPP2R1A mutation affects the ability of some B-subunits to interact and form the PP2A complex. We have also shown that PP2A may interact with novel proteins such as NPM1 and histones. Ongoing work will be completed to determine how these interactions function in the context of ovarian and endometrial carcinomas. Citation Format: Melissa K. McConechy, Vincent Chen, Gregg Morin, James Brenton, David G. Huntsman. PPP2R1A mutations affect PP2A complex formation, and novel protein interactions in gynecological carcinoma cell lines. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A25.
Reply from Author re: Alberto Briganti, Niccolò M. Passoni, Firas Abdollah, Alessandro Nini, Francesco Montorsi, R. Jeffrey Karnes. Treatment of Lymph Node–Positive Prostate Cancer: Teaching Old Dogmas New Tricks. Eur Urol 2014;65:26–8
Authors: Karim Touijer
Journal: European Urology (2013)
Aspartame and its effects on health: Authors' reply
Authors: Michael E J Lean, Catherine R Hankey
Journal: BMJ (2005)

Save the FDAEditor-Abbasi asks whether drug regulation is failing. 1 The US Food and Drug Administration (FDA) performs a thankless task.Patients want new drugs available immediately and agitate to accomplish this.Patients also wish medicines to be guaranteed safe, and blame the FDA when toxicity leads to a drug's withdrawal.Clinical scientists complain that the FDA obstructs their investigations.Pharmaceutical companies see the FDA as an adversary, not a protector.Practising in the USA for 20 years, I encountered many FDA agents.A few revered regulations for their own sake.Such people are irksome, but without strict oversight valueless and toxic agents would be marketed.A prime example is Laetrile (laevo-mandelonitrile-beta-glucuronoside), a useless and poisonous drug promoted for cancer treatment.The FDA, supported by the National Cancer Institute, successfully resisted extreme public pressure to allow its marketing, saving many lives and a multimillion dollar fraud.The FDA faces serious accusations.Attempting to suppress David Graham's whistleblowing on rofecoxib assaults scientific honesty. 2 3 The FDA's refusal to allow non-prescription sales of emergency contraception indicates unacceptable political pressure from the religious right.Unduly close relations between the FDA and pharmaceutical companies may lead to premature marketing approvals.How should the FDA be saved?Firstly, officials ordering withdrawal of a drug should be independent of those who approve marketing.Secondly, making the FDA a quango would protect from political pressures.Thirdly, conflicts of interest involving FDA employees and consultants must be rigorously scrutinised, even more severely than editors scrutinise the interests of contributors.The UK's Medicines and Healthcare products Regulatory Agency is accused of proindustry bias.Housecleaning there and at the FDA will benefit patients, doctors, and the pharmaceutical industry itself.
Leucine aminopeptidase in the pancreatic juice during ethionine pancreatitis
Authors: K. Muller-Wieland
Journal: Gut (1964)

EDITORIAL SYNOPSIS In the early stages of ethionine pancreatitis leucine aminopeptidase output was increased while the excretion of amylase, trypsin, and lipase was diminished.Muller-Wieland and Becker (1962) have reported an increase of leucine aminopeptidase in the duodenal juice of man after stimulating the exocrine pancreas.The present experiments were designed to investigate the pattern of leucine aminopeptidase output in normal rats and in animals poisoned with ethionine.METHODS Pancreatic juice was withdrawn from 41 male albino rats ranging in weight from 200 to 300 g. in an acute experi- ment.The exocrine pancreas was stimulated by secretin and pancreozymin (Boots).The technical details have already been described in full (Muller-Wieland, 1964).The activity of the enzymes amylase (Norby, quoted by Lagerlof, 1942) trypsin (Gowenlock, 1953), lipase (Marchis-Mouren, Sarda, and Desnuelle, 1959), and leucine aminopeptidase (Goldbarg and Rutenburg, 1958) was estimated in fractions of pancreatic juice.Pancreatitis was caused by ethionine.Male rats only were used, because of the excessive fatty degeneration of the liver in female rats in the early stage of ethionine toxicity (Farber, Koch-Weser, and Popper, 1951; Becker 1957). RESULTS CONTROLSIn six animals the standard errors of the mean for volume, and output of amylase, trypsin, lipase, and leucine aminopeptidase were, in the secretin period, 8 13, 7 57, 10-7, 6-68, and 9 25 %, and in the pancreozymin period 12-6, 12 7, 10-7, 11*2, and 5-82%.The relationship of enzyme output during the post-secretin and post-pancreozymin phases was 5-56:1, 2-95:1, 2-43:1, and 2-40:1 (Table I).INCREASING DOSES OF ETHIONINE (EXPERIMENTAL GROUPS 1-5) In rats given from 0-33 to 100 mg./g.body weight of ethionine the volumes of the pancre-
Inhibition of Adenoma Progression to Adenocarcinoma in a 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis Model in A/J Mice by Tea Polyphenols and Caffeine
Authors: Gang Lu, Jie Liao, Guangyu Yang, Kenneth R. Reuhl, Xingpei Hao, Chung S. Yang
Journal: Cancer Research (2006)

Abstract The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (−)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)–induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation. (Cancer Res 2006; 66(23): 11494-501)
Further Observations on the Effects of Autonomic Blocking Agents in Patients with Hypertension
Authors: DAVID GROB, WILLIAM R. SCARBOROUGH, ALBERT A. KATTUS, HERBERT G. LANGFORD, BARBARA ZIEGLER, SALLE LORE, GRACE SALTZER, MARION BIRMINGHAM
Journal: Circulation (1953)

Moderate reduction in blood pressure by intravenous hexamethonium or pentamethonium was accompanied by a decrease in stroke volume, cardiac output, and left ventricular work, and no change or an increase in peripheral resistance. Renal blood flow, filtration rate, and potassium clearance fell promptly, but returned to the original levels within one to two hours despite continued reduction in blood pressure. Sodium clearance and urine flow were reduced to a greater extent and returned more slowly. Oral hexamethonium produced some reduction in renal blood flow, and improvement in the ballistocardiogram. Oral hydrazinophthalazine diminished the effect of hexamethonium on renal blood flow.
Anti-epiligrin (laminin 5) cicatricial pemphigoid and lung carcinoma: coincidence or association?
Authors: G.E. GIBSON, M.S. DAOUD, M.R. PITTELKOW
Journal: British Journal of Dermatology (1997)

Anti-epiligrin cicatricial pemphigoid (CP) is a rare subset of CP in which patients have IgG autoantibodies directed against the dermal side of skin split by 1 mol/L NaCl. The antibodies react against epitopes in the lowermost portions of the lamina lucida, and immunoprecipitate epiligrin (laminin 5) in human keratinocyte extracts. We report a patient with this uncommon form of CP, who, following an 8-year period of well-controlled disease, experienced a severe flare in symptoms coincident with development of lung carcinoma. This raises the possibility of an association, in this case, between anti-epiligrin CP and lung carcinoma.
Peter John Verrill
Authors: Nigel Dacre, John Verrill
Journal: BMJ (2006)

​FormerFormer consultant anaesthetist and dean University College London (b 1930; q University College London 1953; DA, FFA RCS), died from postoperative complications following a sigmoid colectomy on 30 June 2006.



Figure 1



A highly respected consultant anaesthetist, Peter Verrill had a long and distinguished association with University College London. He started as an undergraduate in 1948, became a consultant in 1963, vice dean of the University College Hospital Medical School in 1964, and dean of the Faculty of Clinical Sciences in 1984. He was elected fellow in 1987, retiring in 1994. He helped to set up a ground breaking pain management clinic, pioneering the use of intravenous diazepam as an anaesthetic in dentistry. Verrill's sign is still used today. As dean, he played an important part in forming the joint University College Hospital/Middlesex School of Medicine. He leaves a wife, Christine; four children; and 13 grandchildren. A memorial service will be held at St Pancras Parish Church, Euston Road, London NW1, on Wednesday 1 November at 2 30 pm.
DISTURBANCES OF BEHAVIOR IN PATIENTS WITH DISSEMINATED SCLEROSIS
Authors: ORTHELLO R. LANGWORTHY, LAWRENCE C. KOLB, SERGE ANDROP
Journal: American Journal of Psychiatry (1941)

Sixteen of 199 cases of disseminated sclerosis which have been the subject of detailed study were admitted to psychiatric hospitals sometime during the course of their illness. The early transient attacks of numbness or palsy are often considered to be hysterical manifestations. Sclerotic plaques often occur in the white matter of the forebrain and may produce mental symptoms. It is important also to take into consideration the fundamental behavior pattern of the individual and the personal reactions to the illness. Emotional instability was the basis for the difficulties which caused many of the individuals to consult a psychiatrist. Often overt sexual activity, sometimes associated with impotency, caused difficulties of adjustment. All patterns of maladjustment have been seen.