tbuckley/cabot-search huggingface dataset:
Abstract LB-257: Profiling the effects of IDH1 and IDH2 mutants on the glioma cell metabolome
Authors: Hai Yan, Zachary J. Reitman, Genglin Jin, Ivan Spasojevic, Yiping He, Darell D. Bigner, Edward D. Karoly, Jian Yang, Kenneth W. Kinzler, Bert Vogelstein
Journal: Cancer Research (2011)

Abstract Somatic hotspot mutations in the NADP+-dependent isocitrate dehydrogenases, IDH1 and IDH2, arise frequently in gliomas. These gliomas include WHO grades II and III oligodendrogliomas and astrocytomas, as well as WHO grade IV secondary glioblastomas. When mutated, IDH1 and IDH2 gain the ability to produce (R)-2-hydroxyglutarate (2HG) and may dominant-negatively inhibit IDH1-WT. Aside from these specific functions, the downstream effect of these metabolic enzyme mutations on cellular metabolism is unknown. To identify metabolic alterations caused by IDH1 and IDH2 mutants, we used three mass spectrometry methods (GC-MS/MS, LC-MS/MS +ESI, and LC-MS/MS -ESI) to profile &amp;gt;200 biochemicals in lysates of human oligodendroglial cell line (HOG) cells that homologously express IDH1-R132H or IDH2-R172K, which are the most frequent IDH1 and IDH2 mutants in glioma, respectively. To determine whether 2HG production or inhibition of IDH1-WT could mediate similar effects on cellular metabolism as IDH mutant expression, we also analyzed cells treated cells with either 7.5mM or 30mM 2HG as well as cells with stable shRNA knockdown of endogenous IDH1-WT. Unsupervised hierarchical clustering, univariate threshold tests, correlation analysis, and principal component analysis revealed that cells expressing IDH1-R132H and IDH2-R172K have similar metabolite profiles, and that 2HG treatment also results in a similar profile. However, cell with shRNA IDH1 knockdown shared few metabolic features with cells expressing IDH mutants. Metabolite set enrichment analyses revealed that numerous amino acids, N-acetylated amino acids, TCA cycle metabolites, glutathione metabolites, and choline derivatives were markedly altered in IDH-mutant expressing cells. Strikingly, we found that N-acetyl-aspartyl-glutamate (NAAG), a common brain metabolite, is 50-fold reduced in cells expressing IDH1-R132H and &amp;gt;2-fold reduced in human glioma tissues with IDH1-R132H compared to glioma tissues without IDH mutations. This work shows that IDH mutants can induce widespread cellular metabolic changes. Additionally, the metabolites that were found to be altered in this study may play a role in glioma pathogenesis and may be useful for diagnosis or treatment for gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-257. doi:10.1158/1538-7445.AM2011-LB-257
Gastric Atrophy and Carcinoid Tumors
Authors: MARK P. CARUSO
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 March 1984Gastric Atrophy and Carcinoid TumorsMARK P. CARUSO, M.D., DONALD BEARDWOOD, M.D., ROBERT MAXWELL, M.D., CHARLES WAGNER, M.D.MARK P. CARUSO, M.D.Search for more papers by this author, DONALD BEARDWOOD, M.D.Search for more papers by this author, ROBERT MAXWELL, M.D.Search for more papers by this author, CHARLES WAGNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-100-3-459_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The description by Carney and associates (1) of the newly identified syndrome of gastric atrophy and multiple carcinoid tumors, has prompted our review of a case seen last year at our institution.A 54-year-old white woman was admitted with weakness and fatigue. The patient had adult onset diabetes mellitus, thyroprivic hypothyroidism, and pernicious anemia from age 35, confirmed by the Schilling test. The patient was being treated for these disorders. She had a serum gastrin value of 9000 pg/mL, and no rheumatoid factor and antinuclear antibodies. A barium roentgenogram showed diminished mucosal markings in the stomach, with...Reference1. CARNEY J, GO V, FAIRBANKS V, MOORE B, ALPORT E, and NORA F. The syndrome of gastric argyrophil tumors and nonantral gastric atrophy. Ann Intern Med. 1983;99:761-6. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MARK P. CARUSO, M.D.; DONALD BEARDWOOD, M.D.; ROBERT MAXWELL, M.D.; CHARLES WAGNER, M.D.Affiliations: Abington Memorial Hospital Abington, PA 19001 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCurrent Gastroenterologic Aspects of Pernicious AnemiaThe Effects of Famotidine, 40 mg at Night, on 24-Hour Intragastric Acidity and Plasma Gastrin Concentration in Healthy SubjectsTwenty-four-hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemiaMULTIFOCAL GASTRIC CARCINOID TUMOURS, ACHLORHYDRIA, AND HYPERGASTRINAEMIACarcinoid Tumor, Atrophic Gastritis, and Iron Deficiency AnemiaMERCEDES BIOSCA, M.D., FERNANDO GARCIA-BRAGADO, M.D., MARIANO DE LA FIGUERA, M.D., JOAQUIN MADRENAS, M.D., ANTONIO SALAS, M.D. 1 March 1984Volume 100, Issue 3Page: 459-459KeywordsAntinuclear antibodiesAtrophyCarcinoid tumorDiabetes mellitusFatigueGastrinHypothyroidismPatientsPernicious anemiaStomach ePublished: 1 December 2008 Issue Published: 1 March 1984 PDF downloadLoading ...
AAV1/2-mediated CNS Gene Delivery of Dominant-negative CCL2 Mutant Suppresses Gliosis, β-amyloidosis, and Learning Impairment of APP/PS1 Mice
Authors: Tomomi Kiyota, Masaru Yamamoto, Bryce Schroder, Michael T Jacobsen, Russell J Swan, Mary P Lambert, William L Klein, Howard E Gendelman, Richard M Ransohoff, Tsuneya Ikezu
Journal: Molecular Therapy (2009)

Accumulation of aggregated amyloid-β (Aβ) peptide was studied as an initial step for Alzheimer's disease (AD) pathogenesis. Following amyloid plaque formation, reactive microglia and astrocytes accumulate around plaques and cause neuroinflammation. Here brain chemokines play a major role for the glial accumulation. We have previously shown that transgenic overexpression of chemokine CCL2 in the brain results in increased microglial accumulation and diffuse amyloid plaque deposition in a transgenic mouse model of AD expressing Swedish amyloid precursor protein (APP) mutant. Here, we report that adeno-associated virus (AAV) serotype 1 and 2 hybrid efficiently deliver 7ND gene, a dominant-negative CCL2 mutant, in a dose–response manner and express >1,000-fold higher recombinant CCL2 than basal levels after a single administration. AAV1/2 hybrid virus principally infected neurons without neuroinflammation with sustained expression for 6-months. 7ND expressed in APP/presenilin-1 (APP/PS1) bigenic mice reduced astro/microgliosis, β-amyloidosis, including suppression of both fibrillar and oligomer Aβ accumulation, and improved spatial learning. Our data support the idea that the AAV1/2 system is a useful tool for CNS gene delivery, and suppression of CCL2 may be a therapeutic target for the amelioration of AD-related neuroinflammation. Accumulation of aggregated amyloid-β (Aβ) peptide was studied as an initial step for Alzheimer's disease (AD) pathogenesis. Following amyloid plaque formation, reactive microglia and astrocytes accumulate around plaques and cause neuroinflammation. Here brain chemokines play a major role for the glial accumulation. We have previously shown that transgenic overexpression of chemokine CCL2 in the brain results in increased microglial accumulation and diffuse amyloid plaque deposition in a transgenic mouse model of AD expressing Swedish amyloid precursor protein (APP) mutant. Here, we report that adeno-associated virus (AAV) serotype 1 and 2 hybrid efficiently deliver 7ND gene, a dominant-negative CCL2 mutant, in a dose–response manner and express >1,000-fold higher recombinant CCL2 than basal levels after a single administration. AAV1/2 hybrid virus principally infected neurons without neuroinflammation with sustained expression for 6-months. 7ND expressed in APP/presenilin-1 (APP/PS1) bigenic mice reduced astro/microgliosis, β-amyloidosis, including suppression of both fibrillar and oligomer Aβ accumulation, and improved spatial learning. Our data support the idea that the AAV1/2 system is a useful tool for CNS gene delivery, and suppression of CCL2 may be a therapeutic target for the amelioration of AD-related neuroinflammation.
Studies must establish whether prolonged QTc interval in newly diagnosed type 1 diabetes is reversible
Authors: P. Kempler, K. Keresztes, Z. Hermanyi, A. Marton
Journal: BMJ (1998)

EDITOR—Naas et al found that the corrected QT (QTc) interval, QT dispersion, and QTc dispersion are accurate predictors of cardiac death in newly diagnosed non-insulin dependent diabetes.1 > QT interval is influenced by many factors, including electrolyte abnormalities, myocardial ischaemia, autonomic imbalance, and alcohol toxicity. Prolongation of the QT interval is related to the severity of autonomic neuropathy in patients with alcoholic and non-alcoholic liver disease.2

We studied 27 patients with newly diagnosed insulin dependent …
Reflex increase in blood pressure during the intracoronary administration of adenosine in man.
Authors: D A Cox, J A Vita, C B Treasure, R D Fish, A P Selwyn, P Ganz
Journal: Journal of Clinical Investigation (1989)

Infusion of adenosine (0.022-2.2 mg/min) into the left anterior descending (LAD) coronary artery of 26 patients produced a dose-dependent increase in blood pressure without a change in heart rate. At adenosine 2.2 mg/min, systolic pressure rose by 21.0 +/- 2.2 mmHg from 134 +/- 4.3 mmHg (P less than 0.001) and diastolic pressure increased by 10.4 +/- 1.1 mmHg from 76 +/- 1.9 mmHg (P less than 0.001). The rise in arterial pressure was associated with a 22 +/- 3.4% increase in systemic vascular resistance (P less than 0.01) and no change in cardiac output (-2.8 +/- 4.3%, P = NS). Plasma norepinephrine levels rose by 40 +/- 14% from 105 +/- 9 pg/ml (P less than 0.05) and epinephrine levels by 119 +/- 31% from 37 +/- 9 pg/ml (P less than 0.01). Right atrial infusion of adenosine produced insignificant hemodynamic effects, suggesting that systemic spillover of adenosine was not responsible for the observed effects. In 20 cardiac transplant patients with denervated hearts, LAD infusion of adenosine (2.2 mg/min) produced no change in systolic pressure (-0.1 +/- 1.6 mmHg from 139 +/- 3.4 mmHg, P = NS) and a decrement in diastolic pressure (-4.7 +/- 1.2 mmHg from 98 +/- 2.5 mmHg, P less than 0.01). Thus, infusion of adenosine into the LAD coronary artery causes a reflex increase in arterial pressure due to a rise in systemic vascular resistance, probably as a result of increased sympathetic discharge. This reflex pathway may be of importance in disease states such as myocardial ischemia, in which myocardial adenosine levels are elevated.
CBFA2T2 and C20orf112: two novel fusion partners of RUNX1 in acute myeloid leukemia
Authors: M C Guastadisegni, A Lonoce, L Impera, F Di Terlizzi, G Fugazza, S Aliano, R Grasso, T Cluzeau, S Raynaud, M Rocchi, C T Storlazzi
Journal: Leukemia (2010)
Exaggerated atrial arachidonate metabolism in rabbit left ventricular myocardial infarction.
Authors: A S Evers, C G Dunkel, J E Saffitz, P Needleman
Journal: Journal of Clinical Investigation (1987)

Isolated perfused rabbit hearts that have previously been subjected to in vivo left ventricular myocardial infarction respond to N-formylmethionyl-leucyl-phenylalanine (fMLP) or bradykinin (BK) administration with the synthesis of large quantities of eicosanoids. To anatomically localize these synthetic responses we studied the effects of fMLP and BK on eicosanoid synthesis in isolated atria and isolated perfused ventricles from normal and infarcted (4 d in vivo) rabbit hearts. These studies revealed that enhanced agonist-stimulated eicosanoid synthesis occurs largely in the right atria of infarcted hearts, a site distant from the zone of injury. Studies of exogenous arachidonate metabolism in microsomes prepared from various regions of the heart showed that while prostaglandin synthetic capacity is preferentially localized to the right atrium, right atria from normal and infarcted hearts have similar thromboxane and PGE2 synthetic capacity. These results demonstrate that enhanced agonist-stimulated eicosanoid synthesis following rabbit left ventricular myocardial infarction occurs largely in the right atrium, and that this effect is independent of the activity of prostaglandin synthetic enzymes.
Nurse specialist in family planning.
Authors: J Newton, G Barnes, J Cameron, P Goldman, J Elias
Journal: BMJ (1976)

In an experimental clinic, run by nurse specialists in family planning, a total of 768 patients were seen in the first year. Oral contraception was dispensed for 377 patients and 187 intrauterine devices (IUCDs) were inserted; a further 204 IUCD patients attended only for follow-up visits. All side effects were adequately diagnosed by the nurse specialist.
GP is struck off for lying to police
Authors: C. Dyer
Journal: BMJ (2009)

A GP who lied to the police and a coroner has been ordered to be struck off the medical register for bringing the profession into disrepute.

Nigel Palmer and his practice manager, Nancy Wainwright, lied to cover up his failure to visit Eileen Gill, 82, before she died in a fire at her home in September 2007.

Her daughter called Barnsley social services from her home in Spain a month before the fire because she was concerned that her mother, who used matches carelessly, might burn the house down.

Social services contacted Dr Palmer’s surgery to …
Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression
Authors: Byoung Kwon Yoo, Luni Emdad, Zao-zhong Su, Augusto Villanueva, Derek Y. Chiang, Nitai D. Mukhopadhyay, Alan Scott Mills, Samuel Waxman, Robert A. Fisher, Josep M. Llovet, Paul B. Fisher, Devanand Sarkar
Journal: Journal of Clinical Investigation (2009)

Hepatocellular carcinoma (HCC) is a highly aggressive vascular cancer characterized by diverse etiology, activation of multiple signal transduction pathways, and various gene mutations. Here, we have determined a specific role for astrocyte elevated gene-1 (AEG1) in HCC pathogenesis. Expression of AEG1 was extremely low in human hepatocytes, but its levels were significantly increased in human HCC. Stable overexpression of AEG1 converted nontumorigenic human HCC cells into highly aggressive vascular tumors, and inhibition of AEG1 abrogated tumorigenesis by aggressive HCC cells in a xenograft model of nude mice. In human HCC, AEG1 overexpression was associated with elevated copy numbers. Microarray analysis revealed that AEG1 modulated the expression of genes associated with invasion, metastasis, chemoresistance, angiogenesis, and senescence. AEG1 also was found to activate Wnt/β-catenin signaling via ERK42/44 activation and upregulated lymphoid-enhancing factor 1/T cell factor 1 (LEF1/TCF1), the ultimate executor of the Wnt pathway, important for HCC progression. Inhibition studies further demonstrated that activation of Wnt signaling played a key role in mediating AEG1 function. AEG1 also activated the NF-κB pathway, which may play a role in the chronic inflammatory changes preceding HCC development. These data indicate that AEG1 plays a central role in regulating diverse aspects of HCC pathogenesis. Targeted inhibition of AEG1 might lead to the shutdown of key elemental characteristics of HCC and could lead to an effective therapeutic strategy for HCC.
Trust's mental health services are threadbare, says CHI
Authors: Roger Dobson
Journal: BMJ (2004)

Mental health services run by a Welsh NHS trust are threadbare and often cannot help patients with urgent needs, an investigation by the Commission for Health Improvement (CHI) has concluded.

Staff shortages have led to heavy dependency on locums and bank staff, and there have been times when patients who needed to be detained or sectioned had been left in the community overnight.

The commission's investigators also found evidence of nurses working 24 hour shifts (by being both permanent and bank nurses), signs of staff burnout, considerable levels of sickness absence, high staff turnover, and concerns about the level of supervision for professional staff. …
Bioequivalence of inhaled drugs
Authors: E Derom, R Pauwels
Journal: European Respiratory Journal (1995)

<h3>Abstract</h3> Sleep loss is associated with increased obesity risk, as demonstrated by correlations between sleep duration and change in body mass index or body fat percentage. Whereas previous studies linked this weight gain to disturbed endocrine parameters after sleep deprivation (SD) or restriction, neuroimaging studies revealed up-regulated neural processing of food rewards after sleep loss in reward-processing areas such as the anterior cingulate cortex, ventral striatum and insula. To tackle this ongoing debate between homeostatic versus hedonic factors underlying sleep loss-associated weight gain, we rigorously tested the association between SD and food cue processing using high-resolution fMRI and assessment of hormones. After taking blood samples from thirty-two lean, healthy men, they underwent fMRI while performing a neuroeconomic, value-based decision making task with snack food and trinket rewards following a full night of habitual sleep (HS) and a night of SD in a repeated-measures cross-over design. We found that des-acyl ghrelin concentrations were increased after SD compared with HS. Despite similar hunger ratings due to fasting in both conditions, participants were willing to spend more money on food items only after SD. Furthermore, fMRI data paralleled this behavioral finding, revealing a food reward-specific up-regulation of hypothalamic valuation signals and amygdala-hypothalamic coupling after a single night of SD. Behavioral and fMRI results were not significantly correlated with changes in acyl, des-acyl or total ghrelin concentrations. Our results indicate that increased food valuation after sleep loss is due to hedonic rather than hormonal mechanisms.
Blood Pressure Measurement in Diabetes Clinic
Authors: Jamie R. Wood, Mary Anno'riordan, Beth A. Vogt, Mark R. Palmert
Journal: Diabetes Care (2006)

The American Diabetes Association statement (1), “Care of Children and Adolescents With Type 1 Diabetes,” outlines recommendations for management of hypertension in children with type 1 diabetes. Hypertension in children can be missed if appropriate norms are not used, and, as the authors state, “clinicians who care for children with diabetes often pay little or no attention to blood pressure.” Here, we report results of a retrospective chart review of serial clinic blood pressure measurements among 217 youth with type 1 diabetes for ≥5 years. Hypertension was defined …
Serum Gamma Glutamyl Transferase and Alanine Transaminase Levels Predict Endothelial Dysfunction in Patients with Non-Alcoholıc Steatohepatitis
Authors: Bahadır Şarlı, Hüseyin Arınç, Ahmet O Baktır, Hayrettin Sağlam, Erkan Demirci, Yasemin Doğan, Serkan Kurtul, Abdulsamet Erden, Ahmet Karaman
Journal: Journal of the American College of Cardiology (2013)
Addition of serum from patients with collagen diseases increases to cultured human endothelial cells production and release of von willebrand factor
Authors: Hideo Kagawa, Susumu Okubo, Koji Iwata, Shosaku Nomura, Kojiro Yasunaga
Journal: American Journal of Hematology (1993)

Abstract The addition of sera from patients with collagen diseases, particularly those with vascular complications, to the supernatant of cultured vascular endothelial cells (EC) in vitro significantly increased the surface and intracellular amounts of von Willebrand factor antigen (vWF:Ag) compared with results obtained with sera from normal healthy subjects. Peak levels of vWF:Ag occurred after 24 h of in vitro culture. Moreover, the amounts of vWF:Ag secreted into the EC supernatant with patient serum added were significantly higher than the amounts secreted into EC supernatant with control serum added, even after 48 h of in vitro culture. Levels of large and intermediate multimers (LIM) of von Willebrand factor (vWF) increased in EC supernatant exposed to serum from patients with collagen diseases as compared with levels in supernatant exposed to serum from normal controls, whereas no significant differences were detected overall between adding the plasma of patients and of normal subjects. In addition, C‐reactive protein (CRP) induced a time‐ and dose‐related release of vWF:Ag from EC, while glucocorticoid did not effect the release of vWF:Ag from EC. These results suggest that the sera of patients with collagen diseases, particularly those with vascular complications, stimulate the production and release of LIM of vWF from EC. © 1993 Wiley‐Liss, Inc.
Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency
Authors: Polina Stepensky, Anne Rensing-Ehl, Ruth Gather, Shoshana Revel-Vilk, Ute Fischer, Schafiq Nabhani, Fabian Beier, Tim H. Brümmendorf, Sebastian Fuchs, Simon Zenke, Elke Firat, Vered Molho Pessach, Arndt Borkhardt, Mirzokhid Rakhmanov, Bärbel Keller, Klaus Warnatz, Hermann Eibel, Gabriele Niedermann, Orly Elpeleg, Stephan Ehl
Journal: Blood (2014)
Reduction of anthralin inflammation by potassium hydroxide and Teepol
Authors: C.M. LAWRENCE, S. SHUSTER, M. COLLINS, J.M. BRUCE
Journal: British Journal of Dermatology (1987)

Application of 1% potassium hydroxide (KOH) reduced subsequent development of anthralin inflammation without loss of its therapeutic effect on psoriasis. Teepol had a similar but smaller effect on subsequent development of inflammation. The action of KOH appears to have resulted from enhanced oxidation of anthralin to inactive products and the action of Teepol to have increased anthralin solubility and removal. The effect of KOH and Teepol decreased with time after anthralin application and both were ineffective by 24 h, indicating that anthralin persists on the skin in an active form for up to 24 h after a single application. The reduction of anthralin inflammation without loss of therapeutic effect is potentially useful in short contact anthralin therapy.
Re: Increased Virus Shedding With Aspirin Treatment of Rhinovirus Infection-Reply
Authors: Edith D. Stanley
Journal: JAMA (1976)

In Reply.—  The following is in response to Drs Griffith and Mogabgab. The normal temperature of the nasal mucosa is 33 to 35 C, which is optimum for rhinovirus cultivation in tissue cultures. In the doses given, the effect of aspirin on thermoregulation is essentially restricted to reducing fever without altering a person's normal nasal temperature (Goodman LS, Gilman A [eds]: The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan & Co, 1970, pp 315-316). Uncomplicated rhinovirus infections in adults do not cause fever; therefore, aspirin should not affect the mucosal temperature. Earlier investigations have shown that lowering the temperature of the nasal turbinates 3 to 5 C by cold exposure had no effect on the susceptibility of persons to infection with common cold viruses ( Am J Hyg 66:59, 1958). Others found no effect on the rate of infection or quantities of virus shed following exposure of volunteers to