tbuckley/cabot-search huggingface dataset:
Relative contribution of T and B cells to hypermutation and selection of the antibody repertoire in germinal centers of aged mice.
Authors: X Yang, J Stedra, J Cerny
Journal: The Journal of Experimental Medicine (1996)

The immune system of aged individuals often produces antibodies that have lower affinity and are less protective than antibodies from young individuals. Recent studies in mice suggested that antibodies produced by old individuals may be encoded by distinct immunoglobulin (Ig) genes and that the somatic hypermutation process in these individuals is compromised. The present study employed Ighb scid mice reconstituted with normal lymphocytes from young (2-3-mo-old) and aged (20-25-mo-old) donors and immunized with a protein conjugate of the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) to determine whether the molecular changes in antibody repertoire reflect senescence in the B cells or whether they are mediated by the aging helper T lymphocytes. The NP-reactive B cells from splenic germinal centers (GC) were recovered by microdissection of frozen tissue sections and their rearranged Ig heavy chain variable region (VH) genes of the V186.2/V3 families were sequenced. It was found that the VH gene repertoire of the GC B cells was strongly influenced by the source of the CD4+ T cells. When T cells were donated by young mice, the anti-NP response in GC was dominated by the canonical V186.2 gene, even if the responder B cells came from aged donors. However, when the mice were reconstituted with T cells from aged donors, the expression of the V186.2 gene by young B cells was diminished and the response was dominated by the C1H4 gene, another member of the V186.2/V3 family. In contrast, the somatic hypermutation process in the GC B cells followed a different pattern. The mutation frequencies in the animals that were reconstituted with both B and T cells from young donors (1/50 to 1/150 bp) were comparable to the frequencies previously reported for NP-immunized intact young/adult mice. However, when either lymphocyte subset was donated by the aged mice, the mutation frequencies declined. Thus, mice reconstituted with T cells from the aged and B cells from the young had severely compromised mutational mechanism. Likewise, the recipients of aged B and young T cells had diminished mutations even though the repertoire of their anti-NP response was dominated by the canonical V186.2 gene. It appears that the change in germine-encoded repertoire and the decrease of somatic hypermutation represent distinct mechanisms of immunosenescence and that the aging of helper T cells plays a pivotal role in both of these processes.
Pediatric Do-Not-Attempt-Resuscitation Orders and Public Schools: A National Assessment of Policies and Laws
Authors: Michael B. Kimberly, Amanda L. Forte, Jean M. Carroll, Chris Feudtner
Journal: The American Journal of Bioethics (2005)

Some children living with life-shortening medical conditions may wish to attend school without the threat of having resuscitation attempted in the event of cardiopulmonary arrest on the school premises. Despite recent attention to in-school do-not-attempt-resuscitation (DNAR) orders, no assessment of state laws or school policies has yet been made. We therefore sought to survey a national sample of prominent school districts and situate their policies in the context of relevant state laws. Most (80%) school districts sampled did not have policies, regulations, or protocols for dealing with student DNARs. A similar majority (76%) either would not honor student DNARs or were uncertain about whether they could. Frequent contradictions between school policies and state laws also exist. Consequently, children living with life-shortening conditions who have DNARs may not have these orders honored if cardiopulmonary arrest were to occur on school premises. Coordinated efforts are needed to harmonize school district, state, and federal approaches in order to support children and families' right to have important medical decisions honored.
Reevaluation of Amiodarone
Authors: Philip J. Podrid
Journal: Annals of Internal Medicine (1995)

Letters15 November 1995Reevaluation of AmiodaronePhilip J. Podrid, MDPhilip J. Podrid, MDBoston University Medical Center; Boston, MA 02118Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-10-199511150-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:I appreciate the comments made by Drs. Ahmed and Goldman and by Dr. Ahmad. They correctly note other toxicities caused by amiodarone not specifically mentioned in my recent review. I recognize that many side effects were not mentioned, but my intent in the review was not to focus on the many toxicities caused by the drug. Its side-effect profile is well known and has been described in several extensive review articles [1-5]. Rather, my purpose was to critically examine the many reported clinical trials in which this agent has been used. Certainly, before any antiarrhythmic drug is administered, ...References1. Raeder EA, Podrid PJ, Lown B. Side effects and complications of amiodarone therapy. Am Heart J. 1985; 109:925-83. Google Scholar2. Wilson JS, Podrid PJ. Side effects from amiodarone. Am Heart J. 1992; 121:158-71. Google Scholar3. Harris L, McKenna WJ, Rowland E, Kickler DM. Side effects and possible contraindications of amiodarone use. Am Heart J. 1983; 106:916-21. Google Scholar4. Naccarelli GV, Rinkenberger RC, Dougherty AH, Fitzgerald DM. Adverse effects of amiodarone. Med Toxicol Adverse Drug Exp. 1989; 4:246-53. Google Scholar5. Mason JW. Amiodarone. N Engl J Med. 1987; 316:455-66. Google Scholar Author, Article, and Disclosure InformationAffiliations: Boston University Medical Center; Boston, MA 02118 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 1995Volume 123, Issue 10Page: 809KeywordsAdverse reactionsClinical trial reportingDrug therapyToxicity ePublished: 15 August 2000 Issue Published: 15 November 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Endothelin receptor is coupled to phospholipase C via a pertussis toxin-insensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells.
Authors: Y Takuwa, Y Kasuya, N Takuwa, M Kudo, M Yanagisawa, K Goto, T Masaki, K Yamashita
Journal: Journal of Clinical Investigation (1990)

The mechanisms of endothelin-1 (ET) actions were investigated in cultured rat aortic vascular smooth muscle A-10 cells. The A-10 cells have a single class of high affinity binding sites for ET with an apparent Mr of 65,000-75,000 on SDS-PAGE. Stimulation of cells with ET induces mobilization of Ca2+ from both intra- and extracellular pools to produce a biphasic increase in cytoplasmic free Ca2+ concentration. ET increases cellular levels of inositol trisphosphate and 1,2-diacylglycerol, indicating activation of phospholipase C by ET. ET stimulates production of inositol phosphates in membranes prepared from A-10 cells in the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S), but not in its absence. Further, specific binding of 125I-labeled ET to A-10 cell membranes is shown to be inhibited by GTP gamma S in a dose-dependent manner. Treatment of A-10 cells with pertussis toxin induces ADP-ribosylation of a 41,000-D membrane protein but fails to block the ET-induced increases in inositol phosphate production and Ca2+ mobilization. These results indicate that the receptor for ET is coupled to phospholipase C via a guanine nucleotide-binding regulatory protein which is distinct from the pertussis toxin substrate in A-10 cells.
Prognostic Significance and Determinants of Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance in Acute Reperfused Myocardial Infarction
Authors: Ingo Eitel, Steffen Desch, Georg Fuernau, Lysann Hildebrand, Matthias Gutberlet, Gerhard Schuler, Holger Thiele
Journal: Journal of the American College of Cardiology (2010)
Common low-density lipoprotein receptor mutations in the French Canadian population.
Authors: E Leitersdorf, E J Tobin, J Davignon, H H Hobbs
Journal: Journal of Clinical Investigation (1990)

Familial hypercholesterolemia (FH) has a frequency of 0.2% in most populations of the world. In selected populations such as the Afrikaners in South Africa, the Christian Lebanese, and the French Canadians, the disease is more frequent due to the founder effect. Previous studies demonstrated that a single mutation at the LDL receptor locus, the so-called French Canadian deletion, makes up 60% of the mutant genes responsible for FH in the French Canadian population. In this study, efforts were directed to determine if there were other common LDL receptor mutations in this population. Three missense mutations were identified and each mutation was reproduced and expressed in vitro. Two of the three mutations result in the production of an LDL receptor protein that is not processed to its mature form at a normal rate. Molecular assays were developed to detect the mutations directly, and the LDL receptor genes of 130 French Canadian FH heterozygotes were screened for the presence of the three missense mutations as well as two deletions. LDL receptor mutations were detected in 76% of individuals and 14% had one of the three missense mutations.
Monitoring and evaluating surgical care: defining perioperative mortality rate and standardising data collection
Authors: Charlotta L Palmqvist, Roshan Ariyaratnam, David A Watters, Grant L Laing, Douglas Stupart, Phil Hider, Joshua S Ng-Kamstra, Leona Wilson, Damian L Clarke, Lars Hagander, Sarah L M Greenberg, Russell L Gruen
Journal: The Lancet (2015)
The Rehnquist Court and Tobacco
Authors: James H. Lutschg
Journal: JAMA (2006)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Relationship between plasma concentrations of N‐terminal pro brain natriuretic peptide and the characteristics and outcome of patients with a clinical diagnosis of diastolic heart failure: a report from the PEP‐CHF study
Authors: John G.F. Cleland, Jacqueline Taylor, Nick Freemantle, Kevin M. Goode, Alan S. Rigby, Michal Tendera
Journal: European Journal of Heart Failure (2012)
Abstract 5467: Green tea catechin intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Authors: Shambhunath Choudhary, Shilpa Sood, Kusum Rathore, Hwa-Chain Robert Wang
Journal: Cancer Research (2012)

Abstract The purpose of our study was to investigate the mechanism by which dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces breast cell carcinogenesis. More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental factors, such as carcinogens in the diet, through a multi-step disease process progressing from non-cancerous to premalignant and malignant stages. The dietary carcinogen PhIP is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically-achievable, pico- to nano-molar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly-acquired, cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis, and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, ERK pathway activation, Nox-1 expression and reactive oxygen species (ROS) elevation. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical, and molecular changes as targeted endpoints, we identified that the green tea catechin components, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity. 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 5467. doi:1538-7445.AM2012-5467
DNA Microarrays Reveal Relationship of Ewing Family Tumors to Both Endothelial and Fetal Neural Crest-Derived Cells and Define Novel Targets
Authors: Martin S. Staege, Christoph Hutter, Ingo Neumann, Sabine Foja, Uwe E. Hattenhorst, Gesine Hansen, Danny Afar, Stefan E. G. Burdach
Journal: Cancer Research (2004)

Abstract Ewing family tumors (EFTs) are small round blue cell tumors that show features of neuroectodermal differentiation. However, the histogenetic origin of EFTs is still a matter of debate. We used high-density DNA microarrays for the identification of EFT-specific gene expression profiles in comparison with normal tissues of diverse origin. We identified 37 genes that are up-regulated in EFTs compared with normal tissues and validated expression of these genes in EFTs by both conventional and quantitative reverse transcription-polymerase chain reaction. The expression pattern of EFT-associated genes in normal tissues indicated a high similarity between EFTs and fetal and neuronal as well as endothelial tissues and supports the concept that a primitive neural crest-derived progenitor at the transition to mesenchymal and endothelial differentiation is transformed in EFTs. EFT-associated genes could be used for molecular discrimination between EFTs and other small round blue cell tumors and clearly identified a cell line (SK-N-MC) that was initially established as neuroblastoma as being an EFT. Ectopic expression of the EFT-specific EWS-FLI1 fusion protein in human embryonic kidney (HEK293) cells was not sufficient to induce the complete EFT-specific gene expression signature, suggesting that the EFT-specific gene expression profile is not just a consequence of EWS-FLI1 expression but depends on the histogenetic background of the EFT stem cell.
Phenolic Compounds in the Treatment of Rheumatic Fever
Authors: NORMAN E. CLARKE, ROBERT E. MOSHER, CHARLES N. CLARKE
Journal: Circulation (1953)

The chemical compounds known to suppress the manifestations of rheumatic fever are reviewed and the antirheumatic nature of certain phenolic compounds discussed. We report on 75 patients with acute rheumatic fever who have been treated with gentisate compounds and discuss the records of 44 of these patients who have been followed for 3 to 20 months after discontinuing drug therapy. These patients were treated with sodium gentisate, "Gen," methyl cellulose-sodium gentisate and gentisic acid ethanolamide. The urinary excretion records of these drugs are given with selected blood level studies. The antihyaluronidase effect of salicylic acid metabolites and the relationship of these phenolic compounds to the pituitary-adrenal axis are discussed.
Skeletal Muscle Is a Primary Target of SOD1G93A-Mediated Toxicity
Authors: Gabriella Dobrowolny, Michela Aucello, Emanuele Rizzuto, Sara Beccafico, Cristina Mammucari, Simona Bonconpagni, Silvia Belia, Francesca Wannenes, Carmine Nicoletti, Zaccaria Del Prete, Nadia Rosenthal, Mario Molinaro, Feliciano Protasi, Giorgio Fanò, Marco Sandri, Antonio Musarò
Journal: Cell Metabolism (2008)
EXTENSIVE PANCREATIC NECROSIS WITH RECOVERY.
Authors: J. F. BALDWIN
Journal: JAMA (1904)

<h3>Introduction.</h3> —At this time, when the attention of the profession is directed so earnestly to the pancreas, the report of the following case, with the lessons to be derived from it, can not fail to be of much interest. <h3>History.</h3> —W. J. G., a practicing physician of Columbus, Ohio, aged 52, had always enjoyed good health until the latter part of August, 1903. About thirty years before he had had some symptoms which led him to suspect the presence of gallstones, but he had been entirely free from the symptoms until six or eight years ago, when he became subject to occasional brief attacks of "indigestion." In August, after eating some ice cream, he had an attack of acute indigestion, with severe pain, vomiting, etc. More or less trouble in the region of the stomach persisted after that time, with several attacks similar to the one in August. During these attacks he
Effects of childhood cancer on long-term survivors and their families.
Authors: B Peck
Journal: BMJ (1979)

Problems experienced by families of long-term survivors of acute lymphatic leukaemia and Wilms9s tumour were investigated to find out the best way of using limited resources to improve management of such patients. All patients had received treatment at Alder Hey Children9s Hospital, and all had completed treatment at least two years before the study. A social worker interviewed the parents of each child. The results showed that various aspects of management needed improvement, including: information given to parents at diagnosis of their child9s illness and during subsequent treatment; continuity of care and multidisciplinary teamwork among those caring for the child; greater understanding by school teachers that such children have the same educational needs as others; wider communication by hospital staff with the child9s other relatives, particularly grandparents; financial help for parents; and marital counselling. To help implement these proposals full-time social workers were attached to the hospital. Preliminary results were encouraging, though it is too early to evaluate the long-term effects of the changes.
Role of Insulin in the Regulation of Leucine Kinetics in the Conscious Dog
Authors: Naji N. Abumrad, L. S. Jefferson, S. R. Rannels, P. E. Williams, A. D. Cherrington, W. W. Lacy
Journal: Journal of Clinical Investigation (1982)

To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 μU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and α-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. l,4,5,[3H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute).
A Triple-Test Plan for the Serologic Diagnosis of Syphilis — A Modern-Day Approach
Authors: Charles M. Carpenter, James N. Miller, Ruth A. Boak
Journal: New England Journal of Medicine (1960)

EXTENSIVE research in the serology of syphilis during the last decade has resulted in the development of a multiplicity of tests, many of which have had limited practical use. Physicians have scarcely been able to keep abreast of the numerous recommended procedures. After brief acquaintance with an alpha-bet-designated test, they are suddenly confronted with another substitute. It is essential that only adequately tested procedures that yield dependable results be advocated.The discovery and development of the Treponema pallidum immobilization test1 has made available to the physician the most effective procedure for differentiating persons with biologic false-positive reactions from patients infected . . .
Utility of Planar Bone Scintigraphy To Distinguish Benign Osteochondromas from Malignant Chondrosarcomas
Authors: HELLE W. HENDEL, SOEREN DAUGAARD, ANDREAS KJAER
Journal: Clinical Nuclear Medicine (2002)

The current study was designed to evaluate the role of planar bone scintigraphy in the diagnosis of sarcomatous change in osteochondromas (cartilaginous exostoses).Histologically verified cases of chondrosarcoma and osteochondroma, in which Tc-99m bone scintigraphy was performed, were reviewed in a retrospective study.Twenty-two cases were evaluated. Of 11 cases with chondrosarcomas, 8 (73%) had clearly increased tracer uptake, whereas the remaining cases had normal or decreased tracer uptake. Of the 11 cases with osteochondromas, 8 (73%) had clearly increased tracer uptake, whereas the remaining cases had normal or decreased tracer uptake. No significant difference in the distribution of scintigraphic results was noted between the two pathoanatomic groups (p = 1).In conclusion, single standing planar bone scintigraphy has no value in distinguishing benign osteochondromas from malignant chondrosarcomas.
Progress towards Millennium Development Goals 4 and 5 on maternal and child mortality: an updated systematic analysis
Authors: Rafael Lozano, Haidong Wang, Kyle J Foreman, Julie Knoll Rajaratnam, Mohsen Naghavi, Jake R Marcus, Laura Dwyer-Lindgren, Katherine T Lofgren, David Phillips, Charles Atkinson, Alan D Lopez, Christopher JL Murray
Journal: The Lancet (2011)