tbuckley/cabot-search huggingface dataset:
METABOLIC IMAGING BIOMARKERS FOR MUTANT IDH1 GLIOMAS
Authors: Sabrina M. Ronen, Jose L. Izquierdo-Garcia, Myriam M. Chaumeil, Larry M. Cai, Joanna J. Phillips, Russell O. Pieper
Journal: Neuro-Oncology (2014)

BACKGROUND: The IDH1 mutation is now recognized as an important driver in the etiology of low-grade brain tumors. In contrast to wild-type IDH1, which catalyzes the conversion of isocitrate to α-ketoglutarate (αKG), mutant IDH1 converts αKG into the oncometabolite 2-hydroxygluatrate (2HG). In an effort to noninvasively image the activity of mutant IDH1, we have previously shown that we can use hyperpolarized αKG together with 13C magnetic resonance spectroscopy (MRS) to noninvasively detect the production of hyperpolarized 2HG in vivo. In more recent studies we have focused on identifying additional metabolic alterations associated with the presence of the IDH1 mutation in order to develop complementary metabolic imaging approaches that might serve to inform on the presence of mutant IDH1 and its modulation with targeted therapies. METHODS: Two mutant and wild-type IDH1 cell models were generated by using either U87 glioblastoma cells or E6/E7/hTERT immortalized normal human astrocytes (NHAs) and lentivirally transducing with either wild-type IDH1 (wt cells) or wild-type and mutant IDH1 (mutant cells). Using 1H MRS we investigated cell extracts to determine steady state metabolite levels. We also determined metabolic fluxes by using 13C MRS and probing the fate of 13C-labeled precursors (at thermal equilibrium or hyperpolarized) in live cells grown in a bioreactor or in orthotopic tumors in rats. RESULTS: We found that in both U87 and NHA-based cell models not only was the IDH1 mutation associated with elevated levels of 2HG, but other metabolite levels were also altered. In particular, steady state glutamate levels were lower. This was associated with an increased flux of glutamine to 2-HG and a concomitantly reduced flux of glutamine to glutamate. The flux of glucose into the TCA cycle and towards glutamate was also reduced. At the same time the activity and expression of BCAT1 and aspartate aminotransferase dropped. Pyruvate dehydrogenase activity was also reduced, associated with an increase in its phosphorylation and the expression of pyruvate dehydrogenase kinase 3. Collectively our findings likely explain the lower glutamate levels observed in mutant IDH1 cells. Importantly, we were also able to detect a drop in the potentially translatable in vivo imaging of hyperpolarized glutamate produced from hyperpolarized αKG in mutant IDH1 orthotopic tumors. CONCLUSIONS: In addition to the production of 2HG, the presence of mutant IDH1 leads to MRS-detectable metabolic changes that could serve as complementary imaging biomarkers of mutant IDH1 activity or its inhibition with treatment. SECONDARY CATEGORY: n/a.
Intramuscular gold decreases cytokine expression and macrophage numbers in the rheumatoid synovial membrane.
Authors: G Yanni, M Nabil, M R Farahat, R N Poston, G S Panayi
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--Cytokines, released from mononuclear cells (MNC) are mediators of joint destruction in rheumatoid arthritis (RA). The mechanisms of action of gold salts used in the treatment of RA are unknown. The aim of this study was to investigate cytokine expression and intensity of MNC infiltrate in the RA synovial membrane (SM) following treatment with sodium aurothiomalate (SAT). METHODS--Sequential blind needle biopsies were obtained at entry into the study and at two and 12 weeks after the start of SAT therapy in 10 patients with active RA. SMs were stained with a panel of monoclonal antibodies to assess cytokine expression (IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and GM-CSF). RESULTS--There was a significant decrease in IL-1 alpha, IL-1 beta, IL-6 and TNF-alpha expression 12 weeks after treatment (p < 0.004, p < 0.002, p < 0.009 and p < 0.004 respectively). This was noted in the lining layer, the perivascular aggregates and the connective tissue areas. Detailed examination of the MNC infiltrate showed a significant reduction in inflammatory monocytes (MONO) in the lining layer at two weeks (p < 0.03). A decrease in the number of CD68+ macrophages (MAC) was noted in the perivascular and connective tissue areas at 12 weeks. No significant changes were observed in the number of T and B cells and blood vessels. CONCLUSION--The results suggest that gold may suppress RA disease activity by diminishing MONO and MAC numbers and consequently monokine production in the SM.
Streptokinase and serum enzyme activity in myocardial infarction.
Authors: F Praetorius
Journal: BMJ (1977)

Streptokinase and serum enzyme activity in myocardial infarctionIn a controlled study of fibrinolytic treatment of unstable angina, Shepherd et all observed rises in serum aspartate and alanine amino- transferase (SGOT and SGPT) activity in eight out of 20 patients.They suggested the liver as the likely sdurce of the increases.I have compared the activity of these two enzymes in patients with myocar- dial infarction who had been receiving streptokinase in almost identi- cal dosage with that used by Shepherd et al. treatment 4-12 hours after onset of symptoms.Bottom: Open circles indicate mean values.
How should we talk to patients with acute leukaemia?
Authors: J A Murray
Journal: BMJ (1981)

It is of more direct interest to the clinical psychiatrist, and so for me poses the most questions.The author gives a brief descriptive account of his wife's serious suicidal impulses in the course of a puerperal psychosis, being apparently unaware that such conditions are well recognised and that effective treatment is available.The terms mental illness, psychosis, and psychiatrist do not appear in the article: it would be appropriate reading for those who talk of the "myth" of mental illness, or of the psychotic person's "right" to refuse care and treatment.This moving account and its conclusion, in ignorance, that medicine knows or cares little about such reactions to childbirth makes one wonder anew how psychiatry can more effectively and acceptably transmit its knowledge and skills to medical and wider audiences.These three papers have pointed valuably to gaps in the current delivery of health care, no doubt in part representing inadequacies in medical education.
Activin induces cell death in hepatocytes in vivo and in vitro
Authors: R Schwall
Journal: Hepatology (1993)

While studying endocrine responses to activin in female rats, we discovered that activin caused a marked reduction in liver mass. The regressed livers exhibited no gross signs of necrosis or infarction, but histopathological evaluation revealed extensive cell death in the centrilobular regions. The dying cells appeared to fragment into structures resembling apoptotic bodies. Liver mass and histological appearance were restored after cessation of activin infusion, indicating that on an organ level, this effect was reversible. To determine whether the effects observed in vivo were caused by direct actions on the liver, we then tested activin on isolated hepatocytes in serum-free medium. Under these conditions, activin caused many hepatocytes to undergo fragmentation, which was accompanied by a loss of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-reducing activity, an index of viability. We compared the effects of activin with those of transforming growth factor-beta because activin is structurally related to transforming growth factor-beta and because transforming growth factor-beta has been shown previously to induce cell death in hepatocytes. Both proteins caused cell death of comparable magnitude, as defined by the extent of loss of MTT-reducing activity, but transforming growth factor-beta was active at one tenth of the effective activin concentrations. A neutralizing monoclonal antibody to transforming growth factor-beta blocked the response to transforming growth factor-beta but had no effect on the response to activin. Conversely, follistatin, an activin-binding protein, blocked the response to activin but not to transforming growth factor-beta. Inhibin, which antagonizes the effects of activin in many systems, had little effect on the response to activin. Activin and transforming growth factor-beta differed in their onset of action; exposure to transforming growth factor-beta for only 1 hr induced a maximal response, whereas maximal response to activin required its continuous presence for 24 hr. These results show a novel effect of activin on cell death in hepatocytes in vivo and in vitro, suggesting that activin may have a previously unrecognized role in regulating hepatic function.
Abnormal intracellular distribution of O6-alkylguanine-DNA-alkyltransferase in hepatitis B cirrhotic human liver: A potential cofactor in the development of hepatocellular carcinoma
Authors: S M Lee, B C Portmann, G P Margison
Journal: Hepatology (1996)

The expression of O6–alkylguanine–DNA–alkyltransferase (ATase), which is responsible for repair of the promutagenic and cytotoxic DNA lesion O6–alkylguanine, was examined by immunostaining in a series of liver sections from normal and hepatitis–B cirrhosis patients using a polyclonal anti–human ATase antiserum. In 10 normal liver sections, the ATase staining was predominantly nuclear and very intense in the majority of the hepatocytes with a panacinar distribution. In contrast, in 15 hepatitis–B sections, the ATase was located mainly in the cytoplasm of the majority of the hepatocytes and had a perinuclear distribution. Scattered hepatocytes showed a more intense staining involving all or part of their cytoplasm; nuclear staining, however, was reduced in intensity, being inconspicuous in seven and patchy and weak in eight. ATase activity in extracts of 10 of the hepatitis–B livers varied from approximately 90 to 360 fmoles/mg protein and there was no apparent relationship between these levels and the cellular distribution of the enzyme. The sequestration of the ATase protein in the cytoplasm, away from its site of action in the cell nucleus suggests that in hepatitis–B cirrhosis, the repair of O6–alkylguanine lesions by ATase may be less efficient than in normal hepatocytes. The abnormal cellular distribution of ATase may thus be an additional cofactor in the development of hepatitis–B–associated hepatocellular carcinoma.
Genetic strategies for mucin metabolism in<i>Bifidobacterium bifidum</i>PRL2010: An example of possible human-microbe co-evolution
Authors: Francesca Turroni, Christian Milani, Douwe van Sinderen, Marco Ventura
Journal: Gut Microbes (2011)

AbstractRecently, we decoded the genome sequence of Bifidobacterium bifidum PRL2010, an isolate originally recovered from a stool sample of a three month old infant. In silico analysis revealed that the the 2,214,650 bp genome of B. bifidum PRL2010 encoded a rich gene repertoire dedicated to the metabolism of host-derived glycans, such as those present in mucin. Whole proteome profiling as well as transcriptomic investigations were used to identify the genetic players and mechanisms responsible for mucin breakdown, revealing a set of chromosomal loci that allow degradation of various O-linked glycans in mucin (such as core 1, core 2, core 3 and core 4 O-glycans). Comparative genomic analyses involving different B. bifidum genomes demonstrated the ubiquitous presence of these genetic regions in genomes of members of this bifidobacterial taxon, and suggest specific B. bifidum metabolic traits that underpin this case of host-microbe co-evolution.This article is related to:
Alcohol Consumption and Breast Cancer Risk
Authors: Andrea Poli
Journal: JAMA (2012)

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
Pharmacodynamics and Pharmacokinetics of Higher-Dose, Double-Bolus Eptifibatide in Percutaneous Coronary Intervention
Authors: Ian C. Gilchrist, J. Conor O’Shea, Teddy Kosoglou, Lisa K. Jennings, Todd J. Lorenz, Michael M. Kitt, Neal S. Kleiman, David Talley, Frank Aguirre, Charles Davidson, John Runyon, James E. Tcheng
Journal: Circulation (2001)

Background Pharmacodynamics of eptifibatide, a cyclic heptapeptide antagonist of platelet glycoprotein IIb/IIIa, are substantially altered by anticoagulants that chelate calcium, resulting in overestimation ex vivo of the in vivo effects of this agent. We conducted a dose-ranging study to characterize the pharmacodynamics and pharmacokinetics of eptifibatide under physiological conditions. Methods and Results Patients (n=39) undergoing elective percutaneous coronary intervention were randomly assigned to an eptifibatide bolus followed by an infusion (180-μg/kg bolus followed by 2 μg/kg per minute or 250-μg/kg bolus followed by 3 μg/kg per minute) for 18 to 24 hours. In a 2:1 ratio, these patients received either a second bolus of eptifibatide (90 μg/kg or 125 μg/kg for the initial 180-μg/kg or 250-μg/kg groups, respectively) or placebo 30 minutes after the initial bolus. Bleeding times, ex vivo platelet aggregation, receptor occupancy, and plasma eptifibatide levels at baseline and at 1, 2, 3, 4, 6, and 8 hours were evaluated. Platelet inhibition was dose dependent and &gt;80% in all groups by steady state. The single-bolus regimens had a transient loss of inhibition at 1 hour, consistent with rapid distribution and drug elimination. Pharmacokinetic modeling suggested that optimal dosing of eptifibatide would be obtained with a 180-μg/kg bolus and a 2-μg/kg per minute infusion followed by a second 180-μg/kg bolus 10 minutes later. Conclusions A novel higher-dose, double-bolus regimen of eptifibatide in coronary intervention attains and maintains &gt;90% inhibition of platelet aggregation in &gt;90% of patients, providing the pharmacodynamic construct for the design of the Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial of adjunctive eptifibatide in coronary stent implantation.
"THE INTRACUTANEOUS GUINEA-PIG TEST FOR HUMAN SUSCEPTIBILITY AND IMMUNITY TO DIPHTHERIA"
Authors: Abraham Zingher
Journal: JAMA (1923)

<h3>To the Editor:</h3> —The tendency to attach names to surgical procedures, to clinical phenomena and to various laboratory tests is exemplified by the second paper of Dr. W. H. Kellogg (The Journal, March 17, 1923, p. 748) describing a "new" test for immunity to diphtheria. This test is a modification of the old established method of Römer's for the intradermal demonstration in the guinea-pig of small amounts of diphtheria antitoxin contained in human serum. Ten years ago I used successfully a similar but more accurate modification of this test, which I described later (<i>J. Infect. Dis.</i>19:557 [Oct.] 1916). These antitoxin tests were made by me to establish some of the fundamental principles in the active immunization with toxin-antitoxin before Dr. Park and I introduced the Schick test as a part of the process of active immunization against diphtheria. We were only too glad to discard the routine use of
Quantitative Molecular Magnetic Resonance Imaging of Tumor Angiogenesis Using cNGR-Labeled Paramagnetic Quantum Dots
Authors: Marlies Oostendorp, Kim Douma, Tilman M. Hackeng, Anouk Dirksen, Mark J. Post, Marc A.M.J. van Zandvoort, Walter H. Backes
Journal: Cancer Research (2008)

Abstract The objective of this study was to develop and apply cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (cNGR-pQDs) for the noninvasive assessment of tumor angiogenic activity using quantitative in vivo molecular magnetic resonance imaging (MRI). cNGR was previously shown to colocalize with CD13, an aminopeptidase that is highly overexpressed on angiogenic tumor endothelium. Because angiogenesis is important for tumor growth and metastatization, its in vivo detection and quantification may allow objective diagnosis of tumor status and evaluation of treatment response. I.v. injection of cNGR-pQDs in tumor-bearing mice resulted in increased quantitative contrast, comprising increased longitudinal relaxation rate and decreased proton visibility, in the tumor rim but not in tumor core or muscle tissue. This showed that cNGR-pQDs allow in vivo quantification and accurate localization of angiogenic activity. MRI results were validated using ex vivo two-photon laser scanning microscopy (TPLSM), which showed that cNGR-pQDs were primarily located on the surface of tumor endothelial cells and to a lesser extent in the vessel lumen. In contrast, unlabeled pQDs were not or only sparsely detected with both MRI and TPLSM, supporting a high specificity of cNGR-pQDs for angiogenic tumor vasculature. [Cancer Res 2008;68(18):7676–83]
Research in Malaria Vaccines
Authors: Louis H. Miller
Journal: New England Journal of Medicine (1986)

The interest in the article1 and letter2 on malaria in this week's Journal stems from developments in research into malarial sporozoites that may lead to an effective vaccine. Anopheline mosquitoes inject sporozoites into humans during a blood meal. Sporozoites rapidly disappear from the blood and enter liver parenchymal cells, where they proliferate during the next 7 to 10 days. Each sporozoite develops into thousands of parasites, each capable of invading an erythrocyte. This initiates the erythrocytic cycle, which causes disease and can lead to death. A vaccine that blocks the entry of sporozoites into liver cells will prevent disease. Immunity . . .
Davis-Christopher Textbook of Surgery: The Biological Basis of Modern Surgical Practice
Authors: B. Eiseman
Journal: JAMA (1973)

David Sabiston has become a Latter-Day Diderot. With the help of 142 distinguished coauthors, he has assembled what may well be the last macrovolume encyclopedia of surgical knowledge. With a biologic-knowledge doubling time of ten years, this book, with its 2,135 pages, has to be the last single-volume compendium in this broad field. Indeed, signs of binary fission are already evident in the availability of Sabiston's work in a two volume set! The editor, reflecting his own philosophy and interest, has asked each author to start his chapter with more than the usual polite bow to the historic tradition of his assigned topic. Some are overly long, but most make interesting reading. If this huge volume had to be de-fatted, this might be a point of partial excision—but historical references add charm to an otherwise almost overwhelming presentation of cold scientific facts. Few surgical textbooks have personality— this one does.
Deep Jaundice in Infectious Mononucleosis
Authors: William P. Corr
Journal: JAMA (1962)

DEEP JAUNDICE in infectious mononucleosis is generally considered rare. It has even been stated that a total serum bilirubin level of over 6 mg/100 ml. makes infectious mononucleosis unlikely. Nevertheless, the presence of fever, pharyngitis, and jaundice in a young person should stimulate the thought of infectious mononucleosis as the "most likely diagnosis, regardless of the level of the bilirubinemia. That this level may be quite high is illustrated by the following case in which a bilirubin level of over 19 mg/100 ml. was observed, and by 10 similar cases, found in the literature, with serum bilirubin levels of 8 mg/100 ml. or more. Case Report A 22-year-old airman was hospitalized on May 21, 1961, complaining of sore throat and backache of 5 days' duration, and of "stomach ache" of 1 day's duration. Five days prior to admission he had developed myalgia, fever, headache, sore throat, and swelling in the
INTRANASAL VIRULENCE OF PNEUMOCOCCI FOR MICE
Authors: Leslie T. Webster, Anna D. Clow
Journal: The Journal of Experimental Medicine (1933)

1. Smooth colony pneumococci fresh from human beings, instilled in small doses into the nasal passages of special mice raised under standard conditions, brought about a characteristic infection and this spread to healthy contacts inciting in them the carrier state or fatal infection. 2. Differences in individual host response to the same dose of a given culture ranged from a complete refractory or nasopharyngeal carrier state, or a local cervical lymphadenitis, to fatal lobular or lobar pneumonias with or without pleurisy, empyema, and pericarditis, and acute fatal septicemia. 3. Pneumococci exhibited consistent individual strain differences with respect to ability to infect, when instilled intranasally into mice, and also differences in the spread to contacts. Degree of intranasal virulence paralleled demonstrable ability to spread to contacts. 4. Degree of intranasal virulence of strains did not parallel intraperitoneal virulence in 50 per cent of strains—high intranasal was accompanied by either high or moderate intraperitoneal virulence, and low intranasal by high, moderate, or low intraperitoneal virulence. 5. Type III strains were of relatively high intranasal and intraperitoneal virulences; Type II strains mostly low in intranasal but high or moderate in intraperitoneal virulence; Type I strains all low in intranasal but either high or moderate in intraperitoneal virulence. Most strains of other types were low both in intranasal and intraperitoneal virulences. 6. The intranasal virulence of pneumococci was not enhanced by animal passage. Nasal passage reduced the intranasal virulence to zero but did not affect intraperitoneal virulence, colony form, and agglutinative specificity. Passage by the intraperitoneal method maintained the characteristic level of intranasal virulence for a period, increased intraperitoneal virulence in some instances, but did not affect colony form or agglutinative properties.
Nudging, Autonomy, and Valid Consent: Context Matters
Authors: Franklin G. Miller, Luke Gelinas
Journal: The American Journal of Bioethics (2013)

Click to increase image sizeClick to decrease image sizeView correction statement:Corrigendum Acknowledgments This commentary is not subject to U. S. Copyright Law. The opinions expressed are those of the authors and do not necessarily reflect the position or policy of the National Institutes of Health, the Public Health Service, or the Department of Health and Human Services.
Scavenger receptor class B type I polymorphisms and peripheral arterial disease
Authors: Andreas Ritsch, Gudron Sonderegger, Anton Sandhofer, Ursala Stanzl, Ivan Tancevski, Philipp Eller, Wilfried Schgoer, Andreas Wehinger, Thomas Mueller, Meinhard Haltmayer, Joseph R. Patsch
Journal: Metabolism (2007)