tbuckley/cabot-search huggingface dataset:
Abstract 215: Mechanisms of p53 activation by NIAM, nuclear interactor of ARF and MDM2
Authors: Sara Reed, Van Tompkins, Jussara Hagen, Katie Thies, Diane Cryderman, Lori Wallrath, Dawn Quelle
Journal: Cancer Research (2012)

Abstract Nuclear interactor of ARF and Mdm2, NIAM, is a novel regulator of the ARF-Mdm2-p53 tumor suppressor pathway. It collaborates with ARF, promotes p53 transcriptional activity, and is negatively regulated by Mdm2-mediated ubiquitination and proteasome degradation. How NIAM activates p53 is not known, however its ability to do so in ARF-null cells reveals it is an ARF-independent process. Our preliminary data suggest that NIAM could activate p53 by either competing Mdm2 away from p53-Mdm2 complexes and/or by inducing lysine 120 acetylation of p53 via the Tip60 acetyltransferase. p53 acetylation at K120 is known to be regulated by two different histone acetyltransferases, Tip60 and MOF, and to promote the specific upregulation of apoptotic genes by p53. Our preliminary data show that NIAM interacts with Tip60 and strongly promotes p53 acetylation of K120, suggesting a functional NIAM-Tip60 interaction in vivo. Tip60 is an established chromatin modifying protein that influences chromatin structure and cancer gene expression. Consistent with these characteristics of Tip60, we discovered that NIAM is a chromatin-associated protein that binds to transcriptionally active regions of the genome. Other findings connect Tip60 and NIAM. Tip60 acts through p53, ARF and Myc to control transcription and promote the DNA damage checkpoint response. We found that NIAM, like Tip60, localizes to sites of DNA repair in response to DNA damage and it is already established that the absence of either protein leads to chromosomal instability. These compelling observations link NIAM with chromatin regulation and DNA damage repair, potentially via Tip60 signaling, all of which are important for the maintenance of chromosomal stability and prevention of cancer. 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 215. doi:1538-7445.AM2012-215
P15 Does an interferon-gamma release assay change practice in patients referred to clinic for possible latent tuberculosis infection?
Authors: J. F. Tiernan, S. Gilhooley, M. E. Jones, J. D. Chalmers, C. McSparron, I. Laurenson, J. Stevenson, A. T. Hill
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Suspected latent tuberculosis infection (LTBI) is a common reason for referral to TB specialist clinics. This is becoming increasingly frequent since the introduction of newer immunomodulatory drugs. Interferon-gamma release assays (IGRAs) are more sensitive and specific than tuberculin skin tests (TSTs) for diagnosing LTBI. NICE guidelines (2011) recommend considering IGRA testing to diagnose LTBI in those with positive TST or in whom TST may be less reliable. The aim of this study is to determine if IGRA changes practice in the management of cases referred to a TB specialist clinic for possible LTBI. <h3>Methods</h3> A prospective study was carried out over a 29-month period. All adult patients who had three interventions [TST, chest x-ray (CXR) &amp; QuantiFeron TB-Gold (QFT)] were included. The original decision to proceed with TB chemoprophylaxis was made by TB team consensus, based on the clinical history and TST alone. Cases were then analysed with the addition of QFT to determine if the QFT had altered management. An independent TB physician subsequently reviewed the cases. Each case was then analysed on the presumption of QFT as a “gold-standard” vs the original clinician-based approach. <h3>Results</h3> 204 patients were included. Sixty-eight were immunocompromised. One hundred and nine were referrals from other medical specialties, with the remaining 95 from other agencies. One hundred and eighteen patients had a positive TST and 84 had a negative TST. In those with positive TST, 35 (30%) had a positive QFT and 83 (70%) had a negative QFT. Practice changed in 77 (65%) cases with positive TST, all of whom avoided TB chemoprophylaxis due to negative QFT. Of the 68 immunocompromised patients, 16 (24%) underwent change of practice (Abstract P15 figure 1). There were no discrepancies between the original team and the independent TB physician. “Gold-standard” analysis revealed 12 discrepant cases (6%). No cases of active TB have developed in the study population, with maximum follow-up period of 36 months. <h3>Conclusions</h3> This study demonstrates a significant change of clinical practice in the management of possible LTBI with the recent introduction of QFT testing. Our findings support the NICE 2011 recommendations with regard to TST-positive patients and immunocompromised patients.
Treatment of Methanol Intoxication by Hemodialysis
Authors: William H. Austin, C. Philip Lape, Harold N. Burnham
Journal: New England Journal of Medicine (1961)

THE effectiveness of the artificial kidney in removing a wide variety of ingested poisons has been demonstrated in recent years.1 , 2 Studies by Marc-Aurele and Schreiner3 have shown the feasibility of artificial dialysis in the treatment of acute methanol intoxication. They demonstrate the removal of methanol from the laboratory animal and suggest that the metabolic by-products — namely, formic acid and formaldehyde — are theoretically dialyzable substances. At this writing we are unable to find case reports of patients with acute methanol intoxication treated by hemodialysis.Case ReportA 32-year-old dockhand was admitted to the Maine Medical Center on September 15, . . .
Mutant huntingtin fragmentation in immune cells tracks Huntington’s disease progression
Authors: Andreas Weiss, Ulrike Träger, Edward J. Wild, Stephan Grueninger, Ruth Farmer, Christian Landles, Rachael I. Scahill, Nayana Lahiri, Salman Haider, Douglas Macdonald, Chris Frost, Gillian P. Bates, Graeme Bilbe, Rainer Kuhn, Ralph Andre, Sarah J. Tabrizi
Journal: Journal of Clinical Investigation (2012)

Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin (HTT). Therapeutic approaches to lower mutant HTT (mHTT) levels are expected to proceed to human trials, but noninvasive quantification of mHTT is not currently possible. The importance of the peripheral immune system in neurodegenerative disease is becoming increasingly recognized. Peripheral immune cells have been implicated in HD pathogenesis, but HTT levels in these cells have not been quantified before. A recently described time-resolved Förster resonance energy transfer (TR-FRET) immunoassay was used to quantify mutant and total HTT protein levels in leukocytes from patients with HD. Mean mHTT levels in monocytes, T cells, and B cells differed significantly between patients with HD and controls and between pre-manifest mutation carriers and those with clinical onset. Monocyte and T cell mHTT levels were significantly associated with disease burden scores and caudate atrophy rates in patients with HD. mHTT N-terminal fragments detected in HD PBMCs may explain the progressive increase in mHTT levels in these cells. These findings indicate that quantification of mHTT in peripheral immune cells by TR-FRET holds significant promise as a noninvasive disease biomarker.
G protein βγ directly regulates SNARE protein fusion machinery for secretory granule exocytosis
Authors: Trillium Blackmer, Eric C Larsen, Cheryl Bartleson, Judith A Kowalchyk, Eun-Ja Yoon, Anita M Preininger, Simon Alford, Heidi E Hamm, Thomas F J Martin
Journal: Nature Neuroscience (2005)
Electrocardiographic Evidence of Left Atrial Hypertension in Acute Myocardial Infarction
Authors: PREMINDRA A.N. CHANDRARATNA, MORRISON HODGES
Journal: Circulation (1973)

The relationship between mean left atrial pressure (LA m ) and P-wave abnormalities in lead V 1 of standard 12-lead electrocardiograms was evaluated in 30 patients with acute myocardial infarction. In each patient pulmonary artery diastolic pressure or pulmonary wedge pressure was measured, and these values were used as an estimate of LA m . Electrocardiograms recorded at the time of the pressure measurements were used for P-wave analysis. Patients with a history of hypertension were excluded from analysis. There was a significant correlation between the magnitude of the P terminal force in lead V 1 (PTF-V 1 ) and the estimated LA m (r = –0.78, P &lt; 0.001). Sixteen patients had a normal PTF-V 1 on admission; 11 of them had a normal LA m . All 14 patients with an abnormal PTF-V 1 (more negative than –0.03 mm-sec) on admission had an elevated LA m (&gt;12 mm Hg). Thus, in 25 of the 30 patients, the PTF-V 1 correctly identified whether the LA m was normal or abnormal on admission. On subsequent days, simultaneous measurements of PTF-V 1 and estimated LA m were made in 27 of the patients. Significant changes occurred in both PTF-V 1 and LA m ; discordant changes were observed on only seven of 56 occasions. Measurement of PTF-V 1 appears to be a useful and reliable estimate of left ventricular filling pressure in patients with acute myocardial infarction.
Acute Esophageal Variceal Sclerotherapy
Authors: Alan W. Larson
Journal: JAMA (1986)

Within 48 hours of variceal hemorrhage, 82 patients were randomly assigned to conventional treatment including balloon tamponade or to conventional treatment supplemented by sclerotherapy. The prerandomization general clinical characteristics of the two groups were similar. Seventy-nine percent of patients were alcoholic and 57% were in Child's class C. In the sclerotherapy group of 44 patients, sclerotherapy was performed twice in 28 patients and thrice in 13 patients over the two weeks of follow-up. The number of patients who rebled was significantly lower in the sclerotherapy group than in the group treated conventionally (23% vs 53%). The number of bleeding episodes also was significantly lower in the sclerotherapy group (15 vs 32). Moreover, blood transfusion requirements were significantly decreased in the sclerotherapy group. This was true even for patients who were bleeding at the time of randomization or who were in Child's class C, but this primarily was because fewer patients who underwent sclerotherapy (10 of 24 vs 18 of 23) required transfusions. Although there was no difference in survival between the two groups, we conclude that sclerotherapy is better than conventional treatment in the acute management of variceal bleeding.
ATP11C is critical for the internalization of phosphatidylserine and differentiation of B lymphocytes
Authors: Mehmet Yabas, Charis E Teh, Sandra Frankenreiter, Dennis Lal, Carla M Roots, Belinda Whittle, Daniel T Andrews, Yafei Zhang, Narci C Teoh, Jonathan Sprent, Lina E Tze, Edyta M Kucharska, Jennifer Kofler, Geoffrey C Farell, Stefan Bröer, Christopher C Goodnow, Anselm Enders
Journal: Nature Immunology (2011)
STUDIES OF THE INORGANIC METABOLISM IN PNEUMONIA WITH ESPECIAL REFERENCE TO CALCIUM AND MAGNESIUM
Authors: Francis W. Peabody
Journal: The Journal of Experimental Medicine (1913)

During pneumonia the metabolism of inorganic substances deviates markedly from the normal. While chlorine, sodium, and calcium are retained in the body, potassium and magnesium are excreted normally or in excess. Two cases showed a definite loss of magnesium to the body in the febrile period. During the period of retention the chlorine content of the blood is distinctly lower than normally, the calcium content is apparently slightly lower, and the magnesium content tends also to be a little lower. The skin is shown, to play no special part in the chlorine retention. Since no organ or organs have been shown to store up large amounts of the retained substances, it is probable that they are spread diffusely throughout the body.
The Penetration of Inorganic Ions Through the Wall of a Tuberculous Cavity
Authors: A. Hallen, V. O. Bjork, E. Odeblad
Journal: Thorax (1959)

<h3>Objectives</h3> As access to antiretrovirals (ARV) increases in developing countries, the identification of optimal therapeutic regimens and prevention strategies requires the identification of resistance pathways in non-B subtypes as well as the surveillance of drug mutation resistance (SDMR) including the trafficking of viral strains between high-risk groups such as commercial sex workers (CSW) and the general population (GP). In this study, the authors evaluated the rate of primary resistance mutations and the epidemiological link between isolates from GP and CSW from Bénin. <h3>Methods</h3> Plasma samples were obtained from 129 HIV-1-infected treatment-naïve individuals. Drug resistance mutations were identified using SDMR list and compared with other resistance algorithms. <h3>Results</h3> No nucleoside reverse transcriptase inhibitor resistance mutations were found. Four patients had non-nucleoside reverse transcriptase inhibitor resistance (K103N, G190A). One patient exhibited protease inhibitors resistance mutation, F53Y. Using the SDMR list, the authors obtained a rate of 3.9% of primary resistance. Nevertheless, the authors observed several mutations not on SDMR list but included in others resistance database, taking those mutations into account, the authors obtained a rate of 15.5%. <h3>Conclusions</h3> Although our results show a low rate of SDMR, this algorithm may underestimate resistance mutations that may impact treatment options in developing countries. Primary resistance rates were similar in CSW and in the GP. Our phylogenetic analysis confirmed the genetic exchange between groups.
Abstract PD10-04: Predictive genomic markers to chemotherapy and adjuvant trastuzumab via whole genome expression DASL profiling in the N9831 adjuvant study
Authors: EA Perez, JE Eckel-Passow, KV Ballman, SK Anderson, EA Thompson, YW Asmann, J Jen, AC Dueck, WL Lingle, GW Sledge, EP Winer, J Gralow, RB Jenkins, MM Reinholz
Journal: Cancer Research (2012)

Abstract Background: Adding adjuvant trastuzumab to chemotherapy for patients (pts) with resected HER2+ breast cancer (BC) improves disease free and overall survival (Perez EA, et al. J Clin Oncol 2011). Understanding which pts are most likely to benefit from these therapies is a goal of our team. Methods: Baseline 1639 annotated tumor specimens from pts enrolled in the phase III N9831 adjuvant trastuzumab trial (NCT00005970) were processed via the &amp;gt;29,000 gene probe DASL technology (Illumina) to identify genomic predictors of pt outcome to Arm A chemotherapy or Arm C chemotherapy plus concurrent trastuzumab. Samples were spotted in 96 well plates, with appropriate replicates. Extensive quality control and internal validation were performed. The association of each gene with recurrence-free survival (RFS) was determined for each treatment arm separately using CoxPH models adjusted for clinical and tumor risk factors. A p &amp;lt; 0.0001 was used to define significance. A geneset analysis (using 408 Kegg/BioCarta genesets) was performed to determine pathways associated with RFS. Results: PRPF4B, EWSR1, BMI1, CNNM1, FOXO4, CLIP2, MCCC1, CHRM2 were found to be significantly associated with RFS for Arm A and AAK1, DAZAP2, TP53INP1, MACF1 and ADHFE1 were associated with RFS for Arm C. The most significant pathway associated with RFS in Arm A was the KEGG hypertrophic cardiomyopathy pathway and for Arm C, the BioCarta pertussis toxin-insensitive CCR5 signaling in macrophage pathway. Conclusions: We have identified 8 genes associated with RFS for pts treated with adjuvant chemotherapy, and 5 genes associated with RFS for pts treated with concurrent trastuzumab and chemotherapy in pts with HER2 early stage BC. In addition, geneset analysis identified BioCarta and Kegg pathways associated with RFS for each arm. Validation in an independent cohort is expected to be completed by the end of 2012. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD10-04.
Differential Profile and Biochemical Effects of Antiautonomic Membrane Receptor Antibodies in Ventricular Arrhythmias and Sinus Node Dysfunction
Authors: Pablo A. Chiale, Inés Ferrari, Evelina Mahler, Marina A. Vallazza, Marcelo V. Elizari, Mauricio B. Rosenbaum, Mariano J. Levin
Journal: Circulation (2001)

Background —The relationship between anti-β-adrenergic (anti-βR) and anti-M 2 -cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated. Methods and Results —We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas’ heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas’ heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-β 1 RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for β 1 ,β 2 -adrenergic receptors (cAMP increment) or M 2 -cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-βRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-βRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol. Conclusions —Our results demonstrate a strong correlation between anti-βRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-βRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.
Ectopic Adrenocorticotropic Hormone Syndrome
Authors: BERNARDO LEO WAJCHENBERG, BERENICE B. MENDONCA, BERNARDO LIBERMAN, MARIA A. ALBERGARIA PEREIRA, PAULO CAMPOS CARNEIRO, ALDA WAKAMATSU, MARVIN A. KIRSCHNER
Journal: Endocrine Reviews (1994)

THE production of hormones and other protein markers by tumors has been an intriguing area of tumor biology. It has become apparent during the last decades that a wide range of endocrine tumors secrete hormones not normally associated with the gland in which the neoplasm arises and that nonendocrine tumors can synthesize and/or secrete polypeptide hormones and other tumor-associated proteins. The production of such tumor markers has come to be referred to as "ectopic" or "inappropriate" when the marker is not obviously associated with the tissue from which the tumor derives. Initially the presence of ectopic hormone secretion caused by cancer was considered as rare or unusual, but with the use of modern techniques of hormone detection these syndromes are felt to be common. Indeed, Odell et al. (1) have postulated that all tumors make POMC and other protein markers. Meador et al. (2) developed the concept that certain tumors of "nonendocrine" tissues can give rise to Cushing's syndrome by secreting an adrenocorticotropic substance.
Clinical Comparison of Methyprylone and Quinalbarbitone as Hypnotics
Authors: T. J. Thomson
Journal: BMJ (1958)

Methyprylone ("noludar"; 2,4-dioxo-3,3-diethyl-5- methyl -piperidine) is a non-barbiturate hypnotic.Stewart (1956) reported that in a dose of 200 mg. it had a hypnotic effect comparable to 100 mg. of either amylo- barbitone sodium or butobarbitone.Lasagna (1956) found that 250 mg. of methyprylone produced results " essentially indistinguishable " from those of 100 mg. of
John Stanislaus Guinan
Authors: M. J Guinan
Journal: BMJ (2003)

General practitioner Blackpool, Lancashire (b County Offaly, Ireland, 1913; q University College Dublin 1938), died from ventricular myocardial hypertrophy and coronary artery atherosclerosis on 5 October 2003.

After qualifying John Guinan emigrated to England in 1938 and joined the Royal Army Medical Corps at the outbreak of the second world war. He served in Iraq, the Middle East, the Western Desert, Italy, and Austria, attaining the rank of major. He bought a practice in 1948 in Bury in Lancashire, where he remained until 1978. On the death of his wife, Anne, in 1977, John retired to Ireland but found it difficult to settle. He started doing locums, one of which took him to Blackpool in 1981, where he continued in practice until the last week before his death. He leaves six children and 17 grandchildren.
Astrocyte-Restricted Ablation of Interleukin-17-Induced Act1-Mediated Signaling Ameliorates Autoimmune Encephalomyelitis
Authors: Zizhen Kang, Cengiz Zubeyir Altuntas, Muhammet Fatih Gulen, Caini Liu, Natalia Giltiay, Hongwei Qin, Liping Liu, Wen Qian, Richard M. Ransohoff, Cornelia Bergmann, Stephen Stohlman, Vincent K. Tuohy, Xiaoxia Li
Journal: Immunity (2010)
Gene expression and secretion of atrial natriuretic peptide by murine macrophages.
Authors: A M Vollmar, R Schulz
Journal: Journal of Clinical Investigation (1994)

An increased expression of atrial natriuretic peptide (ANP) has been reported in activated macrophages of the acutely involuted rat thymus. We communicate here that ANP may reflect a common constituent of macrophages, as mRNA coding for ANP is present in peritoneal- as well as in bone marrow-derived macrophages (PM, BMM). Furthermore, both types of macrophages synthesize and release ANP which was found to mainly represent the biologically active fragment ANP99-126. ANP expression in macrophages is regulated by compounds affecting the activity of these immune cells. For example, incubation of PM or BMM in vitro with LPS and zymosan, respectively, increased ANP-mRNA up to sixfold as determined by competitive PCR quantification. Exposure of macrophages to dexamethasone (Dex, 10(-7) M) elicits moderate effects (1.4-fold), while PMA (10(-7) M) failed to affect its abundance. These findings are complemented by data regarding ANP synthesis and secretion. Incubation of macrophages with LPS, Dex or a combination of both results in an up to 3.5-fold increase of intracellular ANP99-126 (basal 10 fmol/mg protein), and an up to 6.6-fold increase of its secretion (basal 40 fmol/mg protein, 24 h). Since macrophages synthesize and release ANP, the peptide may be involved in the complex mechanisms of host defense, a major function of these immune cells.
328 HIERARCHY OF TUMOR AND VIRUS-SPECIFIC CD8 T CELL RESPONSES IN HBV-INFECTED PATIENTS WITH HEPATOCARCINOMA
Authors: A.J. Gehring, Z.Z. Ho, A.T. Tan, M.O. Aung, K.H. Lee, K.C. Tan, S.G. Lim, A. Bertoletti
Journal: Journal of Hepatology (2008)
Intrapancreatic Aneurysm
Authors: Adrian Lambert
Journal: JAMA (1960)

Aneurysms of the pancreatoduodenal or gastroduodenal artery are uncommon lesions, and reports in the literature attest to their extreme rarity. 1 It is the purpose of this report to review a successful operative attack on such a lesion in a patient who survived and was symptom-free 15 months later.  Report of a Case  A 50-year-old man initially presented himself at the first surgical division at Bellevue Hospital on Jan. 24, 1958. He complained of vague intermittent pain in the upper part of the abdomen of a non-specific nature which had been present for one year. In the past he had been told to go on a low-fat diet, which, however, had not relieved the symptoms. There was nothing in the history to suggest further disease. His story included a previous heavy alcoholic intake and an undetermined loss of weight.  The only finding of note in the physical examination made when