tbuckley/cabot-search huggingface dataset:
Abstract 4815: Cytomegalovirus enhances glioblastoma via PDGF-B/STAT3 pathway activation
Authors: Richard L. Price, Jieun Song, Katherine Bingmer, JiYeun Yi, Andreana Rivera, Michael Ogelsbee, Charles Cook, Chang-Hyuk Kwon, E. Antonio Chiocca
Journal: Cancer Research (2012)

Abstract Recently several groups have demonstrated cytomegalovirus (CMV) protein and DNA in a large majority of glioblastomas (GBMs), though the exact role of CMV in tumors remains controversial. Although CMV is capable of activating several oncogenic pathways, it has never been shown to be a transforming virus. Because of this, we hypothesize that CMV infection can modify the rate of gliomagenesis in the context of genetic mutations known to predispose to tumor formation. To test this, we used the Smith strain mouse CMV (MCMV) to infect Mut3 (GFAP-cre; Nf1loxP/+; Trp53-/+) mice that develop normally but eventually develop spontaneous gliomas at an adult age After intraperitoneal viral inoculation, mice exhibited multisystemic infection throughout the body, including the brain. Mut3 mice infected perinatally (103 plaque forming units) developed gliomas significantly sooner than mock-infected Mut3 mice. MCMV-infected mice developed GBMs (WHO grade IV) at a higher rate than less severe tumors, whereas, mock-infected mice developed less severe gliomas (WHO grade III). Since MCMV preferentially infected the neural stem cell (NSC) niche, an area shown to generate gliomas, we interrogated changes in signaling in this population via microarray of cultured NSCs in MCMV- versus Mock-infected mice. Ingenuity Pathway Analysis identified a PDGF-B network as the highest scoring differentially regulated network between MCMV-and Mock-infected neurospheres. In vitro infection of mouse tumorspheres and human GBM tumorspheres with CMV validated the observed upregulation of PDGF-B, a molecule shown to cause gliomas de novo. Additionally, in vitro infection of human glioma stem cells with HCMV (Towne strain) or exogenous PDGF-B activated STAT3, a key regulator of gliomas. In mice infected with MCMV, PDGF-B is upregulated in CA2/3 neurons and STAT3 is activated in the subventricular zone and dentate gyrus suggesting a paracrine effect of MCMV-induced PDGF-B. Also, infected human brain tumor stem cells demonstrated an increase in proliferation via flow cytometry. Taken together, our data suggest that CMV in gliomas may accelerate GBM progression by activating PDGF-B/STAT3 signaling in the NSC population. 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 4815. doi:1538-7445.AM2012-4815
<i>CDKN2A</i>Mutations in Multiple Primary Melanomas
Authors: Jose Monzon, Ling Liu, Herbert Brill, Alisa M. Goldstein, Margaret A. Tucker, Lynn From, John McLaughlin, David Hogg, Norman J. Lassam
Journal: New England Journal of Medicine (1998)

Germ-line mutations in the CDKN2A tumor-suppressor gene (also known as p16, p16INK4a, and MTS1) have been linked to the development of melanoma in some families with inherited melanoma. Whether mutations in CDKN2A confer a predisposition to sporadic (nonfamilial) melanoma is not known. In some patients with sporadic melanoma, one or more additional primary lesions develop, suggesting that some of these patients have an underlying genetic susceptibility to the cancer. We hypothesized that this predisposition might be due to germ-line CDKN2A mutations.We used the polymerase chain reaction, single-strand conformation polymorphism analysis, and direct DNA sequencing to identify germ-line mutations in the CDKN2A gene in patients with multiple primary melanomas who did not have family histories of the disease. A quantitative yeast two-hybrid assay was used to evaluate the functional importance of the CDKN2A variants.Of 33 patients with multiple primary melanomas, 5 (15 percent; 95 percent confidence interval, 4 percent to 27 percent) had germ-line CDKN2A mutations. These included a 24-bp insertion at the 5' end of the coding sequence, three missense mutations (Arg24Pro, Met53Ile, and Ser56Ile), and a 2-bp deletion at position 307 to 308 (resulting in a truncated CDKN2A protein). In three families, CDKN2A mutations identical to those in the probands were found in other family members. In two families with mutations, we uncovered previously unknown evidence of family histories of melanoma.Some patients with multiple primary melanomas but without family histories of the disease have germ-line mutations of the CDKN2A gene. The presence of multiple primary melanomas may signal a genetic susceptibility to melanoma not only in the index patient but also in family members, who may benefit from melanoma-surveillance programs.
Deciding who needs thrombolysis. Disappearing ST elevation could mean reperfusion.
Authors: J Byrne
Journal: BMJ (1993)

conclusions regarding the sensitivity and specificity of electrocardiographic criteria for myocardial infarction in their study therefore remains in doubt.Receiver operator characteristic curves should aim for the highest accuracy because of their value in portraying grades of diagnostic uncertainty, the therapeutic implications of diagnostic uncertainty being especially important in the risk:benefit analysis of potentially dangerous drug treatments.In this context, ST segment elevation should continue to be used as a precondition for thrombo- lytic treatment because of evidence that streptokinase given within two hours of the onset of chest pain produces the most beneficial effects on left ventricular function and survival in the subset of patients with a sum of ST segment elevation of 1*2 mV.
Nucleolin Stabilizes<i><i>Bcl-XL</i></i>Messenger RNA in Response to UVA Irradiation
Authors: Jack Zhang, George Tsaprailis, G. Tim Bowden
Journal: Cancer Research (2008)

Our laboratory has previously reported that UVA irradiation can increase the expression of Bcl-X(L), an antiapoptotic molecule, by stabilizing its mRNA in cultured immortalized human keratinocytes. To understand the mechanism by which the Bcl-X(L) message is stabilized, we used a synthetic Bcl-X(L) 3'-untranslated region (UTR) to capture RNA-binding proteins. Nucleolin was identified as one of the binding proteins as determined by tandem mass spectrometry coupled to liquid chromatography analysis. Further study showed that nucleolin specifically recognized the AU-rich elements (AUUUA) in the 3'-UTR of the Bcl-X(L) mRNA and could stabilize the mRNA in vitro. Furthermore, overexpression of nucleolin stabilizes the Bcl-X(L) mRNA in HeLa cells, whereas reducing nucleolin by small interfering RNA shortens the Bcl-X(L) mRNA half-life. Interestingly, nucleolin physically interacted with polyadenylate [poly(A)]-binding protein through it RGG motifs. Its stabilizing effect on the Bcl-X(L) mRNA was dependent upon the presence of poly(A) tail. Based on these data, we propose a model in which nucleolin protects the Bcl-X(L) mRNA from nuclease degradation by enhancing the stability of the ribonucleoprotein loop structure.
Biomarker profiling of steroid-resistant acute GVHD in patients after infusion of mesenchymal stromal cells
Authors: L C J te Boome, C Mansilla, L E van der Wagen, C A Lindemans, E J Petersen, E Spierings, K A Thus, K Westinga, M Plantinga, M Bierings, A E C Broers, M L H Cuijpers, G W van Imhoff, J J Janssen, C Huisman, S Zeerleder, G Huls, J J Boelens, N M Wulffraat, I C M Slaper-Cortenbach, J Kuball
Journal: Leukemia (2015)
Pertussis Vaccine Encephalopathy-Reply
Authors: Marie R. Griffin
Journal: JAMA (1990)

<h3>In Reply.—</h3> We agree that our data do not prove DTP immunization never causes encephalopathy; our study of 38 171 children with 107154 immunizations did not have sufficient power to detect rare events. However, the consistency of our findings with those of two other recent controlled studies of this question<sup>1,2</sup>led us to comment that if there are encephalopathies caused by DTP immunization, they must be rare. We disagree with the presumption of Tilelli and Manniello that it is established that DTP immunization can cause encephalopathies. Uncontrolled case reports and observations by individual pediatricians do not constitute a scientific basis for establishing causality. The information cited from the 1986 "Redbook"<sup>3</sup>is based on the British National Childhood Encephalopathy Study; recent reanalysis of these data<sup>4</sup>have cast doubt on the original finding of an association between DTP immunization and permanent neurological damage. Thus, the extant data are
Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature
Authors: Yael Haberman, Timothy L. Tickle, Phillip J. Dexheimer, Mi-Ok Kim, Dora Tang, Rebekah Karns, Robert N. Baldassano, Joshua D. Noe, Joel Rosh, James Markowitz, Melvin B. Heyman, Anne M. Griffiths, Wallace V. Crandall, David R. Mack, Susan S. Baker, Curtis Huttenhower, David J. Keljo, Jeffrey S. Hyams, Subra Kugathasan, Thomas D. Walters, Bruce Aronow, Ramnik J. Xavier, Dirk Gevers, Lee A. Denson
Journal: Journal of Clinical Investigation (2014)

Interactions between the host and gut microbial community likely contribute to Crohn disease (CD) pathogenesis; however, direct evidence for these interactions at the onset of disease is lacking. Here, we characterized the global pattern of ileal gene expression and the ileal microbial community in 359 treatment-naive pediatric patients with CD, patients with ulcerative colitis (UC), and control individuals. We identified core gene expression profiles and microbial communities in the affected CD ilea that are preserved in the unaffected ilea of patients with colon-only CD but not present in those with UC or control individuals; therefore, this signature is specific to CD and independent of clinical inflammation. An abnormal increase of antimicrobial dual oxidase (DUOX2) expression was detected in association with an expansion of Proteobacteria in both UC and CD, while expression of lipoprotein APOA1 gene was downregulated and associated with CD-specific alterations in Firmicutes. The increased DUOX2 and decreased APOA1 gene expression signature favored oxidative stress and Th1 polarization and was maximally altered in patients with more severe mucosal injury. A regression model that included APOA1 gene expression and microbial abundance more accurately predicted month 6 steroid-free remission than a model using clinical factors alone. These CD-specific host and microbe profiles identify the ileum as the primary inductive site for all forms of CD and may direct prognostic and therapeutic approaches.
Prevention of Autoimmunity by Targeting a Distinct, Noninvariant CD1d-reactive T Cell Population Reactive to Sulfatide
Authors: Alex Jahng, Igor Maricic, Carlos Aguilera, Susanna Cardell, Ramesh C. Halder, Vipin Kumar
Journal: The Journal of Experimental Medicine (2004)

Class I and class II MHC-restricted T cells specific for proteins present in myelin have been shown to be involved in autoimmunity in the central nervous system (CNS). It is not yet known whether CD1d-restricted T cells reactive to myelin-derived lipids are present in the CNS and might be targeted to influence the course of autoimmune demyelination. Using specific glycolipid-CD1d tetramers and cloned T cells we have characterized a T cell population reactive to a myelin-derived glycolipid, sulfatide, presented by CD1d. This population is distinct from the invariant Vα14+ NK T cells, and a panel of Vα3/Vα8+ CD1d-restricted NK T cell hybridomas is unable to recognize sulfatide in the presence of CD1d+ antigen-presenting cells. Interestingly, during experimental autoimmune encephalomyelitis a model for human multiple sclerosis, sulfatide-reactive T cells but not invariant NK T cells are increased severalfold in CNS tissue. Moreover, treatment of mice with sulfatide prevents antigen-induced experimental autoimmune encephalomyelitis in wild-type but not in CD1d-deficient mice. Disease prevention correlates with the ability of sulfatide to suppress both interferon-γ and interleukin-4 production by pathogenic myelin oligodendrocyte glycoprotein-reactive T cells. Since recognition of sulfatide by CD1d-restricted T cells has now been shown both in mice and humans, study of murine myelin lipid-reactive T cells may form a basis for the development of intervention strategies in human autoimmune demyelinating diseases.
Angioplasty in Acute Myocardial Infarction
Authors: Thomas J. Ryan
Journal: New England Journal of Medicine (1987)

In this issue of the Journal, Topol and the members of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group1 provide another critical piece of information that is destined to influence present trends in the management of acute myocardial infarction. Their multicenter randomized trial showed no additional improvement in ventricular function when balloon angioplasty carried out immediately after successful thrombolytic therapy was compared with a more elective procedure timed to be performed before hospital discharge. Both surprising and important, these findings provoke a desire to consider the background and the future of angioplasty in patients with acute infarction. . . .
Delayed Treatment of Pneumonia and Meningitis
Authors: Robert C. Noble
Journal: Annals of Internal Medicine (1991)

Letters1 May 1991Delayed Treatment of Pneumonia and MeningitisRobert C. Noble, MDRobert C. Noble, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-9-809_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:Delays in the treatment of community-acquired pneumonia and bacterial meningitis were documented in patients admitted to the University of Kentucky Medical Center, a 461-bed teaching hospital. Patients with a positive culture from a cerebrospinal fluid specimen obtained on hospital day 1 were considered to have community-acquired meningitis (1). Infants with meningitis in the first week of life, patients with hospital-acquired meningitis, and patients who previously had received antibiotics were excluded. Patients with a presumed diagnosis of pneumonia were included for study if they were not being treated with antibiotic therapy at the time of admission and if...References1. BryanReynoldsCrout CKL. Promptness of antibiotic therapy in acute bacterial meningitis. Ann Emerg Med. 1986;15:544-7. CrossrefMedlineGoogle Scholar2. McGeeBaringer ZJ. Acute meningitis. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and Practice of Infectious Diseases. 3d ed. New York: Churchill Livingstone; 1990:741-55. Google Scholar3. NahataArnotoPowell MRD. Management of pediatric patients with bacterial meningitis in the emergency department. Drug Intell Clin Pharm. 1986;20:796-8. CrossrefMedlineGoogle Scholar4. TalanGutermanOverturfSingerHoffmanLambert DJGCJB. Analysis of emergency department management of suspected bacterial meningitis. Ann Emerg Med. 1989;18:856-62. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: University of Kentucky College of Medicine Lexington, KY 40536-0084 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPreventing Mismanagement of Community-Acquired Pneumonia at an Urban Public Hospital 1 May 1991Volume 114, Issue 9Page: 809-809KeywordsAntibioticsBacterial meningitisCerebrospinal fluidInfantsMeningitisPneumonia Issue Published: 1 May 1991 PDF DownloadLoading ...
Effects of Carotid Sinus Nerve Stimulation on the Coronary Circulation of the Conscious Dog
Authors: STEPHEN F. VATNER, DEAN FRANKLIN, ROBERT L. VAN CITTERS, EUGENE BRAUNWALD
Journal: Circulation Research (1970)

Control of the coronary circulation by the carotid sinus was studied in intact, unanesthetized dogs instrumented with Doppler ultrasonic flow probes on the left circumflex coronary artery, miniature pressure gauges in the aorta, and stimulating electrodes on the carotid sinus nerves. A radiofrequency pacemaker was used to stimulate the nerves in dogs at rest, during sleep, exercise, and after autonomic blockade. Thirty-second periods of stimulation in the resting conscious dog resulted in an average decrease in aortic pressure of 28%, an average decrease in mean coronary flow of 7%, while heart rate decreased by 13% at the beginning of stimulation and then returned to control levels. Mean and late diastolic coronary resistances decreased by an average of 22% from control. Similar results occurred with carotid sinus nerve stimulation during sleep and during treadmill exercise. Combined beta-receptor blockade with propranolol and atropine prevented the changes in heart rate with carotid sinus nerve stimulation but not the decrease in arterial pressure or the coronary dilatation. After alpha-receptor blockade with phenoxybenzamine or sympathetic blockade with guanethidine, coronary dilatation was not observed with carotid sinus nerve stimulation. Thus sympathetic constrictor tone is present in the resting conscious dog and the coronary dilatation observed with electrical stimulation of the carotid sinus nerves is due to a reduction in resting sympathetic constrictor tone.
Multimodality therapy of an acquired factor V inhibitor
Authors: Yang-Xin Fu, Richard Kaufman, Amy E. Rudolph, Steven E. Collum, Morey A. Blinder
Journal: American Journal of Hematology (1996)

Acquired inhibitors of factor V are rare causes of clinical bleeding, whose severity ranges from mild to life-threatening. Optimal treatment of patients with factor V inhibitors is uncertain. We report on our successful treatment approach in a patient with spontaneous, life-threatening intracranial bleeding caused by a factor V inhibitor. The patient deteriorated after initial treatment with fresh-frozen plasma and platelet transfusions. He was subsequently treated with a combination of plasma exchange and chemotherapy, which led to complete recovery. Our experience suggests that plasma exchange may be life-saving in cases of severe bleeding caused by factor V inhibitors. The use of plasmapheresis in conjunction with chemotherapy is an efficacious and well-tolerated treatment and should be considered in patients with factor V inhibitors.
The Thoracic Duct
Authors: ADOLPH J. RABINOVITZ, OTTO SAPHIR
Journal: Circulation (1965)

In a search for atheromata, multiple sections of thoracic ducts from 119 autopsied individuals, varying in age from newborns to 91 years, were studied histologically with various stains, including fat stains on frozen sections of 84 different ducts. No atheromata were found. Changes in the wall of the duct apparently related to aging included increasing density, minimal intimal fibrosis, degenerative changes in the internal elastic plate, and the appearance of occasional microscopic fibrous polypoid projections into the lumen. Although fat was demonstrated with ease in the wall of the duct and did not appear to be related to the intimal fibrosis, it appeared to be passing through the wall of the vessel without exciting either inflammatory reaction or fibrosis. The findings in the thoracic duct were evaluated with respect to the conventionally accepted definitions of atherosclerosis and phlebosclerosis. It was concluded that the sclerotic changes found in the thoracic duct are more like phlebosclerosis and unlike atherosclerosis in that they bear no relationship to lipid infiltration and reaction thereto. The term "lymphatic sclerosis" was suggested for the condition. The common presence of lipid in the wall of the thoracic duct without reaction and without true atheroma formation indicates that factors beyond mere lipid infiltration of vascular walls must play an important role in the pathogenesis of atherosclerosis.
Comparison of the effects of radiographic contrast media on dehydration and filterability of red blood cells from donors homozygous for hemoglobin A or hemoglobin S
Authors: Patricia Losco, Gerard Nash, Phil Stone, John Ventre
Journal: American Journal of Hematology (2001)

Iodinated radiographic contrast media have traditionally been contraindicated in patients with sickle cell disease because their high osmolality may induce osmotic shrinkage of red blood cells, impair blood flow through the microcirculation, and precipitate or exacerbate a sickle cell crisis. This study investigated that concept by comparing the hematological and rheological effects in vitro of four X-ray contrast media of differing osmolalities: Visipaque (290 mOsm/kg), Hexabrix (600 mOsm/kg), Omnipaque (844 mOsm/kg), and RenoCal-76 (1940 mOsm/kg). Blood was tested from 10 normal and 10 sickle cell donors at drug concentrations of 0, 1, 10, and 30% w/v in an attempt to approximate the relative concentrations of contrast medium to blood that might occur during the bolus-injection and circulation-diluted phases of drug administration. Parameters evaluated included hematology, red cell morphology, and red cell flow resistance through a micropore filter to approximate the microcirculatory effects. Significant hematological effects for both normal and sickle cell donors included a concentration dependent decrease in hematocrit and MCV, and increase in MCHC, all of which varied directly with the osmolality of the contrast media in the order of RenoCal-76 > Omnipaque > Hexabrix > Visipaque. The contrast media had minor effects on red blood cell morphology except for RenoCal-76, 10-30% in which marked echinocytosis was observed. There was no significant increase in the number of irreversibly sickled cells in donors with hemoglobin S. Filterability of red cell suspensions through capillary size pores was impaired in both normal and sickle cell samples in direct proportion to the osmolality of the contrast media, as listed above. Filterability effects were greater for sickle cells than for normal red cells. Visipaque, which was closest to isotonicity, had little effect on red cell volume and had no significant effect on filterability of normal or sickle cells. These results suggest that microcirculatory impairment following infusion of contrast media may occur in sickle patients because of the unusual rheological sensitivity of HbSS red cells, and may be avoided by choice of an isotonic medium.
Optimal Concentration Of Dermatophagoides Pteronyssinus allergen Extract (Dp) For Skin Prick Testing (SPT) In Thai Population With Allergic Rhinitis (AR)
Authors: P. Prottasan, C. Bunnag, P. Tantilipikorn, T. Suwanwech, N. Visitsunthorn, O. Jirapongsananuruk, P. Pacharn, P. Vichyanond
Journal: Journal of Allergy and Clinical Immunology (2012)
Physiological Disposition of 4-C14-Cortisol During Late Pregnancy1
Authors: Claude J. Migeon, Jean Bertrand, Patricia E. Wall
Journal: Journal of Clinical Investigation (1957)

study without interfering with the production of steroid.endogeneous METHODS Preliminary study on newborn infants.If, following the injection of radioactive material to a mother, a large part of the dose were to cross the placenta, we had to be assured that the newborn would dispose of the com- pound as rapidly as do normal adults (10-13).Therefore, in a first step of the present study, we measured the urinary excretion of radioactivity during the 48-hour period following the administration of a minimal dose 4-C -CORTISOL DISPOSITION IN LATE PREGNANCY
GW25-e5318 The research on changes of cardio-pulmonary function and antioxidation of lab rat caused by 105dB noise under different exercise stress training
Authors: Liu Yuanyuan, Yan Jixi, Huang Yuanxun, Wu Xia, Tan Xiaoyu, Zeng Xiangying, Huang Yuanqiao
Journal: Journal of the American College of Cardiology (2014)