tbuckley/cabot-search huggingface dataset:
Abstract LB-411: RNA sequencing reveals CUX1 to be a conserved tumor suppressor in acute myeloid leukemia associated with loss or deletion of chromosome 7
Authors: Megan E. McNerney, Christopher D. Brown, Xiaoyue Wang, Subhradip Karmakar, Chaitanya Bandlamudi, Shan Yu, John Anastasi, Michelle M. Le Beau, Kevin White
Journal: Cancer Research (2012)

Abstract Loss of chromosome 7 and del(7q) [-7/del(7q)] are recurring cytogenetic abnormalities in acute myeloid leukemia (AML), occurring in 9% of de novo AML and 50% of therapy-related myeloid neoplasms (t-MN). Abnormalities of chromosome 7 carry an adverse prognosis. Despite intensive analysis by many laboratories, and the identification of multiple minimally deleted regions on 7q, the putative tumor suppressor(s) on chromosome 7 is currently unknown. We performed transcriptome sequencing on 22 samples and SNP array analysis on 35 samples from patients with myeloid neoplasms, half of which contain -7/del(7q). Copy number analysis identified a 2.17 Mb commonly deleted segment on chromosome band 7q22.1 containing CUX1, a gene encoding a homeodomain-containing transcription factor normally expressed highly in hematopoietic stem cells. CUX1 was found to be disrupted in a translocation resulting in a chimeric RNA fusion transcript in one patient. We found the CUX1 transcript and protein to be expressed at haploinsufficent levels in -7/del(7q) leukemias. To test the tumor suppressor activity of CUX1, the drosophila homologue, CUT, was knocked-down in Drosophila melanogaster hemocytes, which led to significantly increased numbers of hemocytes and melanotic tumor formation. Restoration of CUX1 expression in a human AML cell line with -7 decreased proliferation. These data indicate that CUX1 is a conserved, haploinsufficient, tumor suppressor that promotes leukemogenesis in -7/del(7q) AML. 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 LB-411. doi:1538-7445.AM2012-LB-411
More Mastectomies: Is This What Patients Really Want?
Authors: Monica Morrow, Jay R. Harris
Journal: Journal of Clinical Oncology (2009)

Breast-conserving therapy (BCT), consisting of breastconserving surgery (BCS) followed by breast irradiation, is a notable success story in oncology. For nearly the entire first half of the 20th century, mastectomy was the standard of care in the United States. Remarkably, it took the mature results from six randomized clinical trials comparing BCT with mastectomy before a 1990 National Institutes of Health Consensus Development Panel concluded that BCS wasthepreferredmethodofprimarysurgicaltherapyforwomenwith early-stage breast cancer. 1 From 1989 to 1995, the percentage of women undergoing BCT increased from 35% to 60% for stage 1 and from 19% to 29% for stage 2 breast cancer. 2,3 BCT has been shown to be associated with improved body image and improved short-term physicalfunctioningcomparedwithmastectomy. 4 Intheeraofsentinel node biopsy, BCS is an outpatient procedure that requires no drains,allowingapromptreturntofullactivity,althoughnecessitating
847 THE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKER, CANDESARTAN AND NONSELECTIVE BETA BLOCKER, PROPRANOLOL COMBINATION THERAPY IN REDUCTION OF PORTAL HYPERTENSION COMPARED TO PROPRANOLOL MONTHERAPY
Authors: M.Y. Kim, S.K. Baik, C.S. Won, J.W. Byun, H.J. Park, H.J. Choi, S.Y. Park, Y.H. Kwon, G.J. Cheon, Y.D. Kim
Journal: Journal of Hepatology (2010)
THE PHYSIOLOGICAL ACTION OF ETHYL BROMIDE AND OF SOMNOFORM
Authors: S. W. Cole
Journal: BMJ (1903)

A METHOD for the rapid estimation of CHCI3 vapour in mix- tures of C0C13 and air by means of the alteration of pressure produced by absorption of the C0HCI3 vapour by olive oil is described in the BRITISH MEDICAL JOURNAL Of July 12th, 1902, and was demonstrated last July to the Physiological Society.'It was then stated that the method is applicable to mixtures of chloroform and air between 2 and IO per ioo, and the state- ment was confirmed by Pro!essor Dunstan for amounts between 3 and 12 per ioo.2The original purpose of the present observations was to test the method for mixtures below 2 per ioo.The actual determinations have been made in this laboratory by Dr. Victor Geets, of Brussels, who has, in prosecuting the inquiry, adopted a very simple method of control, which is in itself a very satisfactory laboratory method for the quantitative estimation of the percentage of chloroform vapour in a mixture of chloroform and air.This method consists in the direct weighing on a chemical balance of a flask of known capacity (circa 500 c.cm.), (a) filled with air, (b) filled with the mixture of chloroform and air.The adequacy of this datum as regards an estimation of percentage will be made clear by the following considera- tions: 500 c.cm. of a I to io per Ioo mixture of chloroform and air implies 5 to 50 c.cm. of 01C)13 vapour, weighing (on the assumption that I gram of liquid CHC13=200 c.cm. 0C1I03 vapour) 25 to 250 mg.minus the weight of the volume of air displaced by the CHC13 vapour.The-weight of a lltre of CHCJ3 vapour at o°C. 32+3+ro06 = 2 xoXo895=5-325 grams.Ditto, of a litre of air=I.293grams.
Analysis of the Presence and Physiological Relevance of Subconducting States of Connexin43-Derived Gap Junction Channels in Cultured Human Corporal Vascular Smooth Muscle Cells
Authors: George J. Christ, Peter R. Brink
Journal: Circulation Research (1999)

Abstract —Subconductance states are a commonly observed feature of gap junction channels. Their overt frequency and consistent appearance in both single and multichannel records have led to speculation that they might be of physiological importance in terms of altering the rate of small solute transfer from cell to cell. Among the connexin gene family, connexin43 (Cx43) is the most ubiquitous connexin that has been shown to generate subconductive states. Therefore, it was the explicit aim of this investigation to more fully evaluate the potential contribution of human Cx43-derived subconducting states to intercellular communication in cultured human corporal vascular smooth muscle cells. To determine the weight of subconductive states in our records, we analyzed amplitude histograms of multichannel and single-channel data during the application of transjunctional voltages larger than expected for physiological conditions but still smaller than transjunctional voltages known to induce lower conductive states (V o &gt;V j ). The data clearly indicated that the subconducting states occupy only a small fraction of the total channel open time. This was reflected by the fact that the average open probability for the subconductive state(s) determined from the 9 records analyzed was ≈2%. Closer inspection of the data revealed that the frequency of subconductive states was actually higher than the frequency of the main state conductance. In summary, recording conditions sufficient for evaluation of the intrinsic gating characteristics of human Cx43-derived gap junction channels have been used. Under these conditions, our data clearly indicate that despite their greater frequency, the duration of subconductance events is so short relative to the main state duration as to render them physiologically insignificant.
Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes
Authors: Pablo Sarobe, Eduardo Huarte, Juan José Lasarte, Ascensión López-Dı́az de Cerio, Nicolás Garcı́a, Francisco Borrás-Cuesta, Jesús Prieto
Journal: Journal of Hepatology (2001)
Role of Antibody and Complement in the Immune Clearance and Destruction of Erythrocytes II. MOLECULAR NATURE OF IgG AND IgM COMPLEMENT-FIXING SITES AND EFFECTS OF THEIR INTERACTION WITH SERUM
Authors: Alan D. Schreiber, Michael M. Frank
Journal: Journal of Clinical Investigation (1972)

A model for the immune clearance and destruction of homologous erythrocytes has been further explored. In this model, every IgM anti-erythrocyte antibody molecule in an antibody preparation was shown to fix Cl. About 2000 IgG antibody molecules were required to form a Cl-fixing site on the guinea pig erythrocyte surface. 60 IgM complement-fixing sites per erythrocyte were required for the immune clearance of IgM-sensitized erythrocytes. This number of sites could be detected by a direct agglutination test. 1.4 complement-fixing sites were required for immune clearance of IgG-sensitized cells, a number of molecules which could not be detected by direct agglutination. This number could, however, be detected with the use of a Coombs antiglobulin reagent. Depletion of the late components of complement (C3-9) with cobra venom was associated with the loss of ability to clear IgM-sensitized cells and a marked deficit in the ability to clear IgG-coated cells. Thus, late (C3-9) components of complement as well as an early component (C4) were required for normal clearance of sensitized erythrocytes. There was no evidence that activation of the alternate pathway of complement action could lead to accelerated erythrocyte clearance. In vitro incubation of IgG and IgM-sensitized erythrocytes in fresh serum led to deposition of C3 and C4 on the erythrocyte surface. IgM-sensitized cells treated in this way had a normal survival. IgM-sensitized cells also were shown to remain Coombs positive after their release from the liver. The evidence suggests that the interaction of an IgM site with fresh serum in vitro and in vivo leads to formation of a site which allows for sequestration of cells in the liver. With continued exposure to serum components, this site is destroyed or inactivated. This serum-dependent inactivation is complement-dependent as shown by the use of EDTA-treated and C4-deficient serum. IgG complement-fixing sites are only partially inactivated by incubation in fresh serum, further emphasizing the differences in the biologic activity of IgM and IgG antibodies.
Pulmonary fibrosis in dyskeratosis congenita with<i>TINF2</i>gene mutation
Authors: Atsuro Fukuhara, Yoshinori Tanino, Taeko Ishii, Yayoi Inokoshi, Kazue Saito, Naoko Fukuhara, Suguru Sato, Junpei Saito, Takashi Ishida, Hiroki Yamaguchi, Mitsuru Munakata
Journal: European Respiratory Journal (2013)

To the Editor: 

Dyskeratosis congenita is a rare inherited disorder of ectodermal dysplasia characterised by the classical mucocutaneous triad of abnormal skin pigmentation, nail dystrophy and leukoplakia [1–3], at least one of which is present in around 80–90% of dyskeratosis congenita cases. Bone marrow failure is another common feature, and a variety of other abnormalities ( e.g. dental, gastrointestinal, neurological, ophthalmic, pulmonary and skeletal) have been also described [1–3]. The main causes of mortality in dyskeratosis congenita are bone marrow failure, pulmonary disease and malignancy [1]. Three modes of inheritance have been recognised: X-linked recessive, autosomal dominant and autosomal recessive [1, 3]. Eight dyskeratosis congenita genes ( DKC1 (dyskeratosis congenita 1), TERC (telomerase RNA component), TERT (telomerase reverse transcriptase), NOP10 (nucleolar protein 10), NHP2 , TINF2 (TERF1-interacting nuclear factor 2), TCAB1 and RTEL1 (regulation of telomere elongation helicase 1)) have already been identified, and their mutations account for ∼60% of all dyskeratosis congenita cases [1]. Among the dyskeratosis congenita genes, mutations in TERC , TERT and DKC1 have recently been reported to be associated with familial pulmonary fibrosis and idiopathic pulmonary fibrosis, and pulmonary fibrosis is recognised as one of the features of dyskeratosis congenita. However, the relationship between mutations in the other dyskeratosis congenita genes and pulmonary fibrosis has not yet been clarified. To the best of our knowledge, this is the first case report describing a dyskeratosis congenita patient with pulmonary fibrosis who had a TINF2 mutation.

A 43-year-old female visited our hospital with cough and progressive dyspnoea. She had never smoked, and had a …
Lidocaine in the Prevention of Primary Ventricular Fibrillation
Authors: K.I. Lie, Hein J. Wellens, Frans J. van Capelle, Dirk Durrer
Journal: New England Journal of Medicine (1974)

To assess the efficacy of lidocaine in preventing primary ventricular fibrillation in acute myocardial infarction a double-blind, randomized study was performed in 212 consecutive patients under the age of 70 years admitted to the hospital within six hours of infarction. Group A (107 patients) received an intravenous bolus injection of 100 mg of lidocaine followed by an infusion of lidocaine (3 mg per minute) for 48 hours. Group B (105 patients) received 5 per cent glucose and water. The groups were comparable in age, sex, site and size of infarction, admission time and mortality rate. Ventricular fibrillation did not occur in Group A but did in nine patients of Group B (p < 0.002). Side effects, including drowsiness, numbness, speech disturbances and dizziness, developed in 16 patients(15 percent). These findings indicate that lidocaine in the dosage given was highly effective in preventing primary ventricular fibrillation, but rigid observation of patients and control of infusion rates are required to decrease the likelihood of side effects. (N Engl J Med 291:1324–1326, 1974)
Evaluating short-read sequence data from the highly redundant, novel transcriptome of Polarella glacialis
Authors: Theodore R Gibbons, Gregory T Concepcion, Tsvetan R Bachvaroff, Charles F Delwiche
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Toward a Practical Renaming of Bullous Pemphigoid and All Its Variants—Reply
Authors: Christiaan V. Bakker, Jorrit B. Terra, Marcel F. Jonkman
Journal: JAMA Dermatology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Novobiocin enhances alkylating agent cytotoxicity and DNA interstrand crosslinks in a murine model.
Authors: J P Eder, B A Teicher, S A Holden, K N Cathcart, L E Schnipper
Journal: Journal of Clinical Investigation (1987)

DNA-DNA crosslinks are the lethal cellular mechanism of bifunctional alkylating agent cytotoxicity. Novobiocin, an inhibitor of DNA topoisomerase II, impairs eukaryotic DNA repair of alkylating agent adducts and may increase the number of adducts and their resultant cytotoxicity in malignant cells. The effect of novobiocin on clonogenic survival and DNA crosslinking due to cisplatin (cDDP) and carmustine (BCNU) was studied. Novobiocin caused synergistic cytotoxicity in Chinese hamster ovary cells exposed to cDDP or BCNU. Novobiocin and cDDP increased the formation of DNA-DNA interstrand crosslinks six-fold greater than cDDP alone. The effect was schedule dependent. Novobiocin and cDDP or BCNU markedly reduced in vivo growth of a murine fibrosarcoma without increased host toxicity. As a modulating agent of cytotoxicity due to DNA-DNA crosslinking, novobiocin may enhance the clinical effectiveness of the alkylating agents in human cancer and offer insight into new therapeutic strategies.
Involvement of Cytokines in the Mechanism of Whole-Body Hyperthermia-Induced Cardioprotection
Authors: Nobushige Yamashita, Shiro Hoshida, Kinya Otsu, Naoyuki Taniguchi, Tsunehiko Kuzuya, Masatsugu Hori
Journal: Circulation (2000)

Background —Hyperthermia increases cardiac tolerance to ischemia/reperfusion injury and activates manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, in myocardium in a biphasic manner. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) induced a biphasic cardioprotection that corresponded to the activation of Mn-SOD. However, a direct association between Mn-SOD activation in myocardium and the acquisition of tolerance to ischemia/reperfusion injury induced by hyperthermia and the involvement of the cytokines in the signal transduction pathway for the hyperthermia-induced cardioprotection have not yet been elucidated. Methods and Results —Hyperthermia was induced in anesthetized rats by placement in a temperature-controlled water bath. At 0.5 and 72 hours after hyperthermia, ischemia was induced by occlusion of the left coronary artery for 20 minutes, followed by reperfusion for 48 hours. Inhibition of the increases in Mn-SOD content and activity 72 hours after hyperthermia by the administration of antisense oligodeoxynucleotides to Mn-SOD abolished the expected decrease in myocardial infarct size. The simultaneous administration of neutralizing antibodies to TNF-α and IL-1β before hyperthermia abolished the biphasic cardioprotection and increase in Mn-SOD activity. Conclusions —The increase in Mn-SOD activity mediated through the production of TNF-α and IL-1β by whole-body hyperthermia is important in the acquisition of early- and late-phase cardioprotection against ischemia/reperfusion injury in rats.
Basal phosphatidylinositol turnover controls aortic Na+/K+ ATPase activity.
Authors: D A Simmons, E F Kern, A I Winegrad, D B Martin
Journal: Journal of Clinical Investigation (1986)

To determine whether basal phosphoinositide turnover plays a role in metabolic regulation in resting rabbit aortic intima-media incubated under steady state conditions, we used deprivation of extracellular myo-inositol as a potential means of inhibiting basal phosphatidylinositol (PI) synthesis at restricted sites and of depleting small phosphoinositide pools with a rapid basal turnover. Medium myo-inositol in a normal plasma level was required to prevent inhibition of a specific component of basal de novo PI synthesis that is necessary to demonstrate a discrete rapidly turning-over [1,3-14C]glycerol-labeled PI pool. Medium myo-inositol was also required to label the discrete PI pool with [1-14C]arachidonic acid (AA). The rapid basal turnover of this PI pool, when labeled with glycerol or AA, was not attributable to its utilization for polyphosphoinositide formation, and it seems to reflect basal PI hydrolysis. Depleting endogenous free AA with medium defatted albumin selectively inhibits the component of basal de novo PI synthesis that replenishes the rapidly turning-over PI pool. A component of normal resting energy utilization in aortic intima-media also specifically requires medium myo-inositol in a normal plasma level and a free AA pool; its magnitude is unaltered by indomethacin, nordihydroguaiaretic acid, or Ca2+-free medium. This energy utilization results primarily from Na+/K+ ATPase activity (ouabain-inhibitable O2 consumption), and in Ca2+-free medium deprivation of medium myo-inositol or of free AA inhibits resting Na+/K+ ATPase activity to a similar degree (60%, 52%). In aortic intima-media basal PI turnover controls a major fraction of resting Na+/K+ ATPase activity.
BMA evidence to the Review Body
Authors: J M T Willoughby
Journal: BMJ (1981)

Digitalis increases phrenic nerve activity and causes hyperventilation. To determine whether this effect on respiration is caused by central drug actions on brainstem respiratory neurons or by peripheral drug actions which increase excitatory afferent drive to central respiratory neurons, digoxin was administered intravenously to cats with or without intact IXth and Xth cranial nerves. Digoxin caused marked increases in phrenic nerve activity in cats with intact afferent cranial nerves, but it had no effect in cats with severed afferent nerves. This suggested that effects of digoxin on respiration depend upon afferent input to respiratory neurons. However, digoxin may have had subliminal effects on central neurons which increased phrenic activity only in the presence of excitatory input. To test this possibility, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the phrenic nerve. Subarrhythmic, arrhythmic or lethal doses of digoxin had no effect on excitatory phrenic responses evoked from the pons. Thus, effects of digoxin on phrenic nerve activity appeared to be due primarily to drug actions on peripheral neural sites which had excitatory influences on respiration.